Toxic Shock, Endotoxemia, and Meningococcus

Question 1

What are superantigens?

Answer 1

Antigens that activate high percentages of immune cells by bypassing usual steps in antigen mediated response
Bind to MHCII molecules and variable B subunit of TCR
Activate up to 20% of all T cells

Question 2

What is secreted in response to superantigens?

Answer 2

Extremely high levels of TNF-a, IL-1, and IL-6 causing the symptoms of TSST

Question 3

What is toxic shock syndrome?

Answer 3

Acute, systemic illness with fever and hypotension due to a bacterial superantigen; causes capillary leak, tissue damage, multiorgan failure, and death

Question 4

What two bacteria most commonly cause TSS?

Answer 4

S. Aureus and S. Pyogenes

Question 5

What are signs and symptoms of TSS?

Answer 5

(Think Sepsis) Fever, confusion, headache, diarrhea, vomiting, photophobia, myalgias, sunburn like rash, pelvic pain, sore throat, and hypotension

Question 6

What is the CDC definition of Staph Toxic Shock?

Answer 6

Fever >102

SBP

Question 7

What is the CDC definiton of Strep Toxic Shock?

Answer 7

Isolation of strep from sterile site

SBP

Question 8

How do you treat TSS?

Answer 8

IV fluids
Identification of the site of infection and removal/debridement
Penicillin G (or Nafcillin or Vanc) + Clindamycin to block toxin production
(Can give IVIG to neutralize superantigen)

Question 9

What is the role of TLRs in the host immune system?

Answer 9

TLRs are Patter Recognition Receptors (PRRs) that recognize Pathogen Associated Molecular Patterns (PAMPs)

Question 10

How many different TLRs are there in humans and what happens when they are ligated?

Answer 10

There are 10 different TLRs
When ligated they release inflammatory cytokines (TNF-a, IL-1, and IL-6) and upregulate costimulatory and adhesion molecules

Question 11

What is Endotoxin and how does it activate the immune system?

Answer 11

Endotoxins (LPS for our purposes) are poisonous substances that come from pathogenic organisms that activate the immune response by binding to TLRs. (TLR4 in the case of LPS)

Question 12

What are the common early symptoms of infection with N. Meningitidis?

Answer 12

Flu-like illness
Fever
N/V
Headache
Decreased concentration
Muscle pain

Question 13

When does infection with N. Meningitidis usually occur?

Answer 13

People in their late teens to early twenties during the winter months

Question 14

What are the classic late symptoms of N. Meningitis?

Answer 14

Hemorrhagic petechial rash near pressure areas
Meningismus (Neck stiffness, pain on flexion, photophobia)
Impaired consciousness

Question 15

How rapidly can symptoms progress?

Answer 15

Often less than 24 hrs, progression to Waterhouse-Friedrichson syndrome is associated with increased release of inflammatory cytokines.

Question 16

How is N. Meningitis diagnosed?

Answer 16

Culture from blood or CSF is the gold standard, the gram stain will show gram negative diplococci within 45 minutes
Bx of skin lesion is more sensitive than CSF

Question 17

What is the treatment for N. Miningitis?

Answer 17

Abx for 10-14 days
Penicillin, Ceftriaxone, Chloramphenicol
Steroids are often needed to help clear infection

Question 18

How can you prevent N. Meningitis infection?

Answer 18

Treat contacts with 2 days of rifampin, IM ceftriaxone, and in adults ciprofloxcin
All 11-12 y/o children should be vaccinated with the MCV4 menningococcal conjugate vaccine and boosted at 16