Other genera of Neisseriacease: Eikenella (E. corrodens is normal flora of URT but causes infections in fistfights/bites)
Kingella (K. kingae is normal flora of URT, can disemminate to cause arthritis/endocarditis
•Gram - •Coccus •Nonmotile •Aerobic
Diagnosis/Labs / Virulence Factors
- Catalase Positive
- Oxidase Positive
- 75% genetic similarity
- Often grow as diplococci / 1. Pilus: allows binding to non-ciliated epithelium
Extension, adhesion, contraction
Binds to non-ciliated first, then ciliated later
Source of antigenic variation
2. Opa proteins
Mediate tight adherence to epithelium
But only N. Gonorrhea become opaque
3. Adhesins à Promote invasion of cell
Vitronectin, fibronectin, heparin sulfate proteoglycan, CEACAM 1,3,5, 6
4. Porin proteins (Por)
Essential to acquire nutrients
Facilitate invasion of epithelium
Interfere with neutrophil function
Promotes resistance to complement
5. IgA Protease Cleaves IgA to inactive Fab and Fc / 6. Peptidoglycan fragments (NAG-NAM)
Decrease mucocilliary clearance & kill ciliated epithelium
7. Iron acquisition proteins
Receptors for: Transferrin, lactoferrin, hemoglobin
Do NOT prpduce siderophores
8. Lipooligosaccharide (LOS)
Similar to LPS but lacks O-antigen polysaccharide
Endotoxin activity which elicits inflammatory response
Responsible for the tissue damage
Serum resistance mechanisms
- Sialyated LOS binds host Factor H
- Porins bind host Factor H and C4bp
- Capsule (N. menigitidis only) is resistant to complement
- èC5-C9 deficient patients are very susceptible
Especially to N. menigitidis infections)
- Often escape intracellular killing by neutrophils
Pathogenesis
1. Invade epithelial cells with pili, adhesions, opa, porins apically
2. Transcytosed to basolateral side
3. Can move laterally between cells
4. Kill epithelial cells
5. Taken up by PMNs but avoid killing
6. Establish infection in subepithelium
Neisseria gonorrheae
Diagnosis/Labs / Symptoms / Pathogenesis/Virulence Factors / Treatment
- Fastidious -> need chocolate agar or Thayer-Martin Agar
- Not encapsulated
Labs
- Urine test unreliable
- PCR often used via endocervical/urethra swab
Epidemiology
- Second most common reported infectious disease in US (probably underreported). Chlamydia is first
- Incidence dropped due to Sulfonamide/Penicillin
- Increased in 1960s due to oral contraception
- Dropped in 1970s due to National Gonorrhea Control Program: increased barrier contraception after HIV epidemic
- Antibiotic-resistant gonorrhea has increased especially recently 2005-2007, especially among homosexuals / - Often asymptomatic, especially in women (50-80% assymptomatic)
- Men more likely to exhibit symptoms (95%) but prevalence is probably similar between sexes
- Can remain asymptomatic for months to years
Reproductive complications
- Pelvic Inflammatory Disease (PID)
- Tubal-factor infertility
- Ectopic pregnancy
Congenital complications
- Blindness, Joint infection, Septicemia
Disseminated infect’s(1-3% women, less men)
Bacteremia
- Skin lesions in 75% of bacteremic
Large variability (Vesicles, bullae, uticaria)
Usually can’t culture bacteria from lesions
Polyarthralgia (via bacteremia too)
- Multiple joints
- Does not appear to be autoimmune / - Transmitted mainly during vaginal/anal sex
- Infects single-cell columnar epithelium
Endocervix for women (Vagina too acidic)
Urethra for men (leads to burning sensation)
- Invade, trancytose, establish infection, kill epithelium.
- Large influx of PMNs, purulent discharge
- With no treatment, can lead to asymptomatic stage – dangerous
45% of women develop ascending infection into fallopian tubes -> get PID
Human study
- Infect men only since women have worse complications
- Type 4 pilus negative strain is virulent
Doesn’t need pilus!
- Transferrin-binding receptor (Tbp) negative strain is NOT virulent (only one so far) / Tetracycline
Doxycycline if coinfected with chlamydia
No vaccine
Immunity rarely develops from infection (antigenic variation)
Neisseria genus / ©2009 Mark Tuttle
•Gram - •Coccus •Nonmotile •Aerobic
Neisseria meningitidis
Diagnosis/Labs / Symptoms / Pathogenesis/Virulence Factors / Treatment
- Not very fastidious
- Ferments glucose and maltose (*unique)
- Encapsulated
Labs
- Culture CSF and Blood – look for high WBC with high PMNs
Must be a sterile site since you can carry
- Agglutination test to determine serotype
- PCR
sacC gene for type A
ctrA gene for non-A (B, C, W, W135)
Epidemiology
- “Meningitis belt”: sub-Saharan Africa
- Seasonal peaks: December/January
- Appears to like dry/cold weather
- More common in very young and college age
Risk groups
- Age (ex. Infants)
- Crowded living conditions (ex. Military, college)
- Complement deficiency
- Recent URT, Smoking / - Incubation period: 3-4 days
- High fever, chills, severe headache, vomiting, confusion & agitation CNS)
- Neck stiffness
- Most infections cause meningitis
- 10-15% die
- Onset of symptoms is ABRUPT
Complications
- 10% lose arm or leg
(bleeding/tissue damage)
- CNS problems
- Deafness
- Stroke
Meningiococcal folminant sepsis
- Septicemia, septic shock
- Fatality rate: 18-53%
- Small petechial lesions/purpuric rash
Waterhouse-Friderichsen syndrome
-> adrenal glands / àTransmitted via respiratory droplets
- 1-40% are carriers (only 1-5% non-epidemic)
Epidemic occurs when new serogroup appears
à B/c these strains are eliminated when they get into the blood
- Ab’s against capsule are protective
- Capsule is most important virulence factor
14 serotypes
90% of disease caused by A, B, C, X, Y, and W135
- Unclear how it crosses the BBB, but capsule probably involved
- Untreated mortality is near 100%
Pathogenesis
- May enter non-ciliated epithelium first and either be transcytosed to basolateral side or return to apical surface for transmission to a new host
- Can also get through epithelium by first being phagocytosed by PMNs – “Trojan Horse”
- Bacteremia -> dissemination
Can cause vascular damage, skin rash
If it crosses the BBB, get meningitis / Vaccine
Menomune
- Appropriate for at-risk individuals, not general population
- Polysaccharide only
T-independent antigen
- 85% effective
NOT long lasting
- Poorly effective in children less than 3
- No serotype B because it can elicit autoimmune response (neurons)
- Conjugate polysaccharide vaccines in development à better because get memory response
Menactra
- 4 Polysaccharides conjugated with diphtheria toxoid
- Also reduces carriage
- Serotype C has been largely eradicated -> herd immunity
- A few recipients developed Guillian-Barre
MCV4 now recommended for all 11-18, high risk
Moraxella catarrhalis
•Gram - •Coccus •Nonmotile •Aerobic
Diagnosis/Labs / Symptoms / Pathogenesis/Virulence Factors / Treatment
Human-specific
Commensal organism à opportunistic
Labs
- Oxidase positive
- Diplococci / - 15-25% of otitis media incidents in US
- 80% of US children get otitis media by 3 years of age
- Repeated bouts can lead to slowing of development / - Causes 30% of bacterial complications in patients with COPD
- 4th leading cause of death in the US / No vaccine
Antibiotic-resistant strains emerging