13 Endotoxin, Neisseria Meningitidis Flashcards
What are 3 important components of endotoxin? And what is the toxic portion of the molecule?
Lipid A (toxic portion!) Core Polysaccharides O-antigen (repeat polysaccharide subunits)
T/F- lipopolysaccharide (LPS) is synonymous with endotoxin?
True
Do enterobacteria have LPS or LOS in the outer membrane?
LPS
Do Neisseria and Haemophilus have LPS or LOS in the outer membrane?
LOS
What’s the mechanism of endotoxin?
Binds TLR=> stimulates proinflammatory mediators, activates clotting factors, stimulates complement pathway=>high TNF is the major pathway of LPS induced hypotension and shock!!
How many people die from LPS or LOS gram negative shock per year in the U.S.?
100,000
Why aren’t antibodies effective against LPS?
- large number of O-side chains
- core region not accessible to antibodies
- lipid A is non-antigenic
T/F- N. meningitidis and N. gonorrhoeae are highly fastidious, fragile during specimen transport, and STRICTLY HUMAN pathogens?
True
T/F- N. sicca, N. lactamica, N. flavescens, N. mucosa are less fastidious and more hardy than N. meningitidis or N. gonorrhoeae?
True
Characteristics of Neisseria? Aerobic?
- Gram negative diplocci (flattened adjacent sides)
- Outer membrane has LOS instead of LPS
- Aerobic (do not ferment maltose, lactose etc.) but prefer CO2 rich environment
- Catalase AND oxidase positive
- Most likely to cause disease in pts w/ inherited complement deficiencies
- Humans are ONLY natural host
What is our natural defense against Neisseria organisms?
Complement
What is an important way to differentiate Neisseria from Moraxella?
Moraxella has similar characteristics to Neisseria except Moraxella is Oxidase NEGATIVE(lecture 15 says positive?)
T/F- Neisseria meningitidis produces an exotoxin?
False- it is an endotoxin mediated disease
Is N. meningitidis encapsulated? What cell component is used to categorize this organism?
Yes it has a polysaccharide capsule distal to the LOS and is categorized according to the antigenicity of this capsule==> 13 distinct serogroups exist.
What is the major virulence factor for N. meningitidis? And what does it do?
Capsule causes significant inflammatory response and protects against phagocytosis
Which N. meningitidis capsule groups most commonly cause disease? In developing countries? In the US?
A, B, C, Y, and W135
A and W135: developing countries (sub-saharan africa), epidemics recur every 8-12 yrs in “meningitis belt”
B and C: cause most cases in the US
T/F- Capsule B is non-immunogenic because it is sialic acid and not recognized as foreign and is similar to the capsule in E. coli that causes neonatal meningitidis?
True
Why is serological identification important in N. meningitidis?
Carrier rates can reach 40-80% when new strains reach a naive population and serological ID allows for tracking of strains during and outbreak
N. meningitidis primarily affects children or adults? What diseases does it cause?
Affects children under 5
Causes meningitidis and meningococcemia (bacteria in bloodstream)
T/F- N. meningitidis is the most common cause of community acquired meningitidis in adults?
False. It is second behind S. pneumonia.
What are symptoms of meningitis?
Early signs: sore throat, STIFF NECK, headache, PURPURIC RASH, drowsiness (young children may show vomiting)
Rapidly progresses to mental state changes, high fever, light sensitivity, positive Kernig’s and Brudzinski’s signs, unconsciousness
What is kernig’s sign? What is Brudzinksi’s sign?
kernig’s: Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees.
Brudzinksi’s: Severe neck stiffness causes a patient’s hips and knees to flex when the neck is flexed.
T/F- Meningococcus colonize the nasopharynx and most often cause disease during the summer
False. They do colonize the nasopharynx but most commonly cause disease during the winter
T/F- N. meningitidis with down regulated capsule or “capsule off” colonizing the nasopharynx is rarely or never associated with disease
True
Disease causing strains of N. meningitidis in the nasopharynx act via which mechanism?
- Hypervirulent strains are “capsule on”
- Pili bind receptors on non-ciliated columnar cells of oropharynx and invade mucous membranes. Do NOT attach to ciliated cells. They attach to specialized epithelial cells. Replicate intracellularly and migrate to sub epithelial space where endotoxin (LOS) is released==>when this occurs they are taken up in the bloodstream
How does meningococcus survive in the bloodstream?
- anti-phagocytic capsule
- serum resistance mediated by capsules, sialylated LOS, special porin (Por)
- protease that cleaves secretory IgA molecules bound to Por proteins
- Iron acquisition systems to overcome nutritional immunity
- type IV pili allow organism to attach to meninges in brain (endotoxin disrupts blood-brain barrier)
T/F- inflammation of leptomeninges allows phagocytes, blood proteins, and Neisseria to enter spinal fluid, and if you see gram neg. diploccoci it is indicative of disease?
True. spinal fluid should be sterile
T/F- unique outer membrane blebs (including LOS) are released spontaneously from meningococcus and lead to hyperendotoxic shock
True. This damages host tissues and causes hemorrhaging of blood into skin and mucous membranes (purpuric rash)
T/F- Even with prompt treatment, the fatality rate of endotoxic shock approaches 40%
False. Fatality rate is less than 10%, however, vision loss, hearing loss may occur in survivors
T/F- meningococcemia is bacteremia due to N. meningitidis may occur with or without meningitis, endotoxin effects occur body-wide and involves multiple organs, bacterial invasion of vascular endothelial cells and leads to small vessel thrombosis
True. Petechial lesions on the trunk and lower extremity are common- LOS or bacteria are attached to vessels.
Circulating meningococcal bacteria can deposit in the respiratory tract and cause pharyngitis, otitis media, epiglottitis, and pneumonia. What serotypes are most likely to do this?
Y an W135 have special virulence factors to colonize the respiratory tract.
T/F- breast fed infants are provided protection to many organisms via maternal antibodies, but N. meningitidis is not one of them.
False. Maternal Anti-body protection is provided.
How do you treat invasive meningococcemia?
1..Penicillin, ampicillin, or chloramphenicol (cheap)
OR
2. cephalosporins (expensive)
T/F- you have a short window to diagnose meningococcemia?
True. Patients commonly feel ill in the morning and with be deathly sick by evening.
T/F- Most cases of meningococal disease occur from outbreaks
False. Most are sporadic, but outbreaks are increasing in frequency (military, college dorms, high schools)
How are meningococcal diseases transmitted? Should you treat the patient’s contacts with prophylactics?
Transmission via droplet infection: kissing, sharing utensils, beverages etc are most common.
Treat “close contacts” (family members and anyone who shares respiratory droplets with patient) with rifampin (cheap, but worry about resistance) or fluroquinolones, cephalosporin (expensive, no risk of treatment failure)
A protein conjugated quadri-valent meningococcal vaccine is available, what is it, what serotypes does it protect against, and who should get it?
- protein conjugated quadri-valent vaccine
- No protection against B serogroup (non-immunogenic capsule). Vaccine includes A, C, Y, W135.
- 11-12 year olds or upon college or high school entry
Is the non-conjugated meningococal vaccine T-dependent or independent?
T-independent against the polysaccharide capsule. Therefore must give boosters. Unfortunately only works short term and not in infants or pre-school children.
T/F- Neisseria grows well on blood agar?
False, it is too fastidious. Must use chocolate agar incubated with CO2
T/F- Chocolate agar culture is the gold standard and Neisseria will show transparent, non-pigmented, non hemolytic colonies
True. However, empiric therapy is needed long before culture results become available (can gram stain blood culture or skin lesions, serotype isolated organisms)
Release of which factors from Neisseria Endotoxin (LOS) are responsible for fever and hypotension?
IL-1, TNF released from macrophages are responsible for this
T/F- endotoxin can cause DIC
True
