2. Describe the offending organism of this case, its morphologic, cultural characteristics  and their normal habitat?

Neisseria meningitides

Human source either a carrier or the one with active disease (Nasopharynx)

Morphology

• Gram negative diplococci with flattened sides "kidney bean shaped", polysaccharide capsule present, not readily seen, but serves as the basis for serotyping.

• Endotoxic lipopolysaccharide complexed with protein in outer membrane

• Capsules and pili

Cultural characteristics

• Fastidious species require enriched media (chocolate agar)

• Meningococcus grows as a transparent, non-pigmented, non-hemolytic colony under conditions of moisture and 5-10% C02. Mediums include blood agar, trypticase soy agar, supplemented chocolate agar, and Mueller Hinton agar.

• Growth enhanced in CO2

• Oxidase positive

Structural characteristics

• Antigenic structure

  • Polysaccharide capsule

    • 9 serogroups. A,B,C,Y,W-135 most important

    • immunogenic except Group B

  • Outer membrane proteins

  • Lipopolysaccaharide

3. What kinds of hosts are susceptible?

Sporadic cases or local outbreaks in young adults

4. How do these organisms gain access to humans?

• Nasopharynx (of a carrier or the one with disease) is a common source

• Respiratory droplets requiring close contact and susceptibility (lack of antibody).

• The majority of persons exposed do not contract the disease, likely due to the limited time exposure. The virulence of the strain, host defense and their interactions determine whether the disease is going to follow.

5. How do they invade and spread in humans? Pathogenicity.

Attachment (respiratory colonization)

• pilus mediated attachment- microvilli of nonciliated nasopharyngeal cells

• Transverse cell in vesicle to submucosa

• Damage ciliated cells

Blood stream survival enhanced by antiphagocytic polysaccharide capsule

Meningeal seeding follows bacteremia.

• Bacterial cell wall components initiate a cascade of complement and cytokine mediated events.

• CNS inflammation generated by cell wall peptidoglycan

• LPS, other bacterial products and its mediated by IL-1 and TNF (host response) 

• Once in CSF, the paucity of antibodies, complement components, and white blood cells allow the bacterial infection to flourish.

Endotoxin mediated activation of complement leading to shock and hemorrhage

6. What defenses humans have against these organisms?

• Neutrophil pahgocytosis 
• Complement mediated bactericidal activity
• Antibody

7. How do these organisms able to overcome human defenses?

Polysaccharide capsule resists neutrophil phagocytosis as well as complement mediated bactericidal activity.

8. What is the end result of this battle between organisms and humans?

Untreated the patient will die either from systemic complications or from diffuse CNS ischemic injury.

Meningitis:

This invasion of meninges by this organism results in

• increased permeability of the blood brain barrier
• Cerebral edema
• Toxic mediators in CSF

Exudates extends throughout the CSF, particularly to basal cisterns

• Damaging cranial nerves

• Obliterating CSF pathways (obstructive hydrocephalus) 

• Impair cerebral blood flow: Change of mental status and decreasing alertness.

• Intracranial pressure increases

• Brain edema progresses

Endotoxin mediated events:

Fulminant meningococcal disease, manifested by endotoxin from the N. meningitides cell wall. 

• DIC (disseminated intravascular coagulation)

• Shock

• Bilateral hemorrhagic destruction of the adrenal glands (Waterhouse-Friderichsen syndrome) may occur.

This patient was started on intravenous penicillin, but over the next six hours he developed large purpuric skin lesions, refractory hypotension and died.  He died of Waterhouse-Friderichsen syndrome

9. What are the symptoms from N. meningitis?

• Headache
• Nuchal rigidity
• Fever and chills
• Photophobia
• Vomiting
• Seizures
• Altered sensorium

10.  What are the physical findings of N. meningitis?

Meningeal irritation

• Nuchal rigidity
• Kernig sign (Passive knee extension elicits neck pain and hamstring resistance)
• Brudzinski sign (Involuntary flexion of hips following passive flexion of neck or single hip)

Papiledema: Raised intracranial tension

Isolated cranial nerve abnormalities

Arthritis

Petechiae and cutaneous hemorrhage

Endotoxic shock

Altered mental status

11. How do you diagnose this infection?

Spinal tap: CSF 

• Glucose and protein
• Cell count and differential
• Gram stain demonstrating Gram-negative diplococci is best.
• Bacterial culture
• Counter immune electrophoresis or latex agglutination may demonstrate meningococcal polysaccharide antigen detected in CSF, blood, or urine. The latter method is good for patients where antibiotics were previously administered, or negative cultures. 

CBC with differential

Blood culture

12. What will be your therapeutic strategy?

• Patients decompensate rapidly, Initiate antibiotic therapy (Penicillin) within 30 minutes of initial encounter.
• Do spinal tap before initiating therapy.
• Treat systemic complications

13. How can you prevent it from spreading to others? Prevent its occurrence?

• Close contacts (family members or equivalent) are 1000 times more likely to contract disease if not already immune. 
  • Prophylaxis is appropriate, with Rifampin 600 mg BID for two days.
• Vaccinate all college students for N.meningitis