Bacterial CNS

1. List the Aerobic, gram-negative bacilli that can infect the CNS

2. Other CNS Bacterial PAthogens

Aerobic, gram-negative bacilli

• Escherichia coli

  • Main virulence factor is the K1 (capsular) antigen

• Acinetobacter baumanii

• Pseudomonas aeruginosa

• Serratia sp.

• Salmonella sp.

---

NOTE:

In addition to neonates, and older adults other at risk (for above listed pathogens) individuals are those who

• Experienced head trauma

• Undergone neurosurgical procedures

---

Other CNS bacterial pathogens

• Staphylococcus aureus

• Coagulase-negative, Staphylococcus sp.

• High risk individuals are those whO have undergone neurosurgical procedures

  • Or those with CSF shunts

• Anaerobic streptococci, Bacteroides sp., Fusobacterium sp.

  • Rare

  • Associated with brain abscess, hematogenous spread

What are the symptoms of Bacterial Meningitis

• >2 yrs old

• newborns, infants

Bacterial Meningitis Symptoms

Symptoms

• Greater than 2 years of age

  • Sudden high fever

  • Stiff neck

  • Severe headache

  • Seizures

  • Sleepiness/difficulty waking

  • Sensitivity to light

  • Skin rash (meningococcal meningitis)

• Newborns, infants

  • High fever

  • Constant crying

  • Excessive sleepiness/irritability

  • Poor feeding

  • Bulge in the soft spot on top of baby’s head (fontanel)

  • Stiffness in baby’s body and neck

---

Pathogenesis

• nasopharyngeal colonization -> mucosal barrier invasion -> blood stream -> meninges -> Subarachnoid space  -> bacteria replicates

Describe Haemophilus influenzae 

• Characteristics

Haemophilus influenzae 

Characteristics:

• Gram-negative rods

• Non-motile

• Facultative anaerobes

• Oxidase positive

• Catalase positive

• Reduce nitrates to nitrites

• Require preformed growth factors:

  • X (hemin), and V (NAD)

Describe Meningitis by H. influenzae type b

• Pts affected

• Symptoms

• Virulence Factor

• Pts Affected:

  • children 3 months to 6 years of age

  • Generally, infants 1 – 23 months old

• Symptoms:

  • Mild respiratory disease w/

    • – Headache

    • – Stiff neck

    • – Brudzinski sign

      • Involuntary flexion of the hip and knee when the neck is bent forward

    • Kernig sign

      • Inability to extend the leg while the hip is flexed to 90 degree

• Virulence factors

  • Capsule (most imp.)

    • a, b, c, d, e, f subtypes (det. By polysaccharide)

  • Immunoglobulin A proteases

  • Adherence by fimbriae

  • Outermembrane proteins and LPS

---

NOTE:

Fimbriae have not been found on isolates of H. influenzae from CSF or blood of patients with invasive form of this disease

• Invade bloodstream by a breakdown in the tight junctions between epithelial cells

Besides meningitis, what other diseases does H. Infl. cause?

Haemophilus influenzae Clinical Manifestations

• Septicemia

• Arthritis

• Epiglottitis

  • Intense edema -> airway obstruction

  • Children age 2 —4 years

• Tracheitis

  • Usually arises after an acute viral respiratory infection

  • Thick secretions -> occlude 

  • Must be differentiated from epiglottitis

List the characteristics of Neisseria meningitidis

Characteristics:

• Aerobic, nonmotile, non-spore forming

• Gram-negative, diplococci

• Cytochrome oxidase positive

• Catalase positive

• Capnophilic

  • Requires CO2

• Culture

  • Chocolate agar

• Requires iron for growth

  • Competes with human host by binding human transferrin

  • Possible reason for being strict human pathogens

Neisseria meningitidis: microscopy

1. Describe the Neisseria meningitidis

   • Virulence Factors

   • MOA

   • STATs

   • Incubation

2. List the Meningococcemia Symptoms

3. List the Meningitis Symptoms

Neisseria meningitidis – Virulence Factors

• Pili (fimbriae)

  • mediate adherence to nasopharyngeal

• epithelial cells

• Capsule

• Receptors for human transferrin

• Endotoxin

• Immunoglobulin A protease

---

Neisseria meningitidis

• MOA:

  •  respiratory droplets -> mucosal surfaces of nasopharynx and oropharynx -> blood stream 

• STATs

  • 30% of the population

  • Military recruits and college students have increased risk of exposure

  • @ risk groups:

    • Infants 1-23 months

    • Children greater than 2 years, adults

    • Older adults greater than 65 years

• Incubation 1 – 10 days

---

Meningococcemia Symptoms

• Purpura of skin and mucous membranes

• Petechial rash

• Tachycardia, hypotension

• DIC (disseminated intravascular coagulation)

---

Meningitis Symptoms

• Headache

• Fever

• Meningismus

  • Inflammation of meninges, or subarachnoid hemorrhaging

  • Nuchal rigidity

  • Kernig’s sign, Brudzinski’s sign

• Altered sensorium

  • Inability to think clearly or concentrate

Streptococcus pneumoniae

1. Streptococcus pneumoniae Characteristics

2. Virulence Factors

3. STATs

4. Pneumococcal meningitis symptoms

• Gram-positive diplococci

• Alpha-hemolytic on blood agar

• Catalase negative

• Optochin sensitive

• Oxidase negative

• Urease negative

• Ferments

  • Glucose

  • Lactose

---

Virulence Factor:

• Polysaccharide capsule

  • Abs can work against this

---

STATs

• Most common cause of meningitis in adults

• Second most common cause of meningitis in children

---

Pneumococcal meningitis symptoms

• Onset is usually rapid

• Chest pain, chills

• Cough, fever

• Confusion, headache

• Stiff neck

Streptococcus pneumoniae

Streptococcus pneumoniae

Describe Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae

• Immune Defense vs Evasion

• Diagnostic

Immune Defense vs Evasion:

• Defense:

  • Ability to adhere to mucosal surfaces can be inhibited by IgA

• Evasion:

  •  Produce IgA proteases -> cleaves hinge region

---

Diagnostics:

• Multiplex bacterial PCR diagnostic assay

  • For All mentioned

• can detect low numbers of bacteria

• Can detect nonviable etiologic agents in pts receiving antimicrobial therapy

• Specificity 99.1 – 100% predictive

Describe Listeria monocytogenes

• Characteristics

• Pathogenesis

• STATs

• High Risk Groups

• Clinical Symptoms

Characteristic

• Gram-positive rods

• Facultative anaerobe

• Catalase positive

• Oxidase negative

• Tumbling motility at 25 degC

• Growth on blood agar

• Exposure from raw vegetables, raw milk, cheese, meats (deli)

---

Pathogenesis

• Ingestion of contaminated foods

  • Consumption of Dairy and processed meats

  • Incubation 11-90 days

• Endocytosis across mucosal barrier -> BBB

  • Hematogenous dissemination

  • predilection for the CNS and placenta

• CNS invasion by 3 methods

  • Invasion of endothelial cells of BBB

  • Transportation -> CNS w/in circulating leukocytes 

    • (phagocyte facilitated)

  • Bacteria inoculated into oral tissues -> macrophage phagocytosis -> invade CNs

---

• STATs

  • Fifth most common cause of meningitis

• High risk groups

  • Neonates (less than 1 month)

  • Older adults (greater than 65 years)

• Clinical symptoms

  • Stiff neck

  • Movement disorders (ataxia, tremors)

  • Seizures

  • Fluctuating mental status

Listeria monocytogenes

Listeria monocytogenes

Streptococcus agalactiae

Streptococcus agalactiae

Describe Streptococcus agalactiae 

• Characteristics

• Virulence Factors

• Risk Groups

• 
  

Characteristics

• Gram-positive cocci

• Normal bacterial flora of the GI/GU 

• Lancefield group – B

• Beta hemolysis

• Bacitracin resistant

• Catalase negative

---

Virulence Factors

• Capsule (imp.)

  • Inhibits 

    • complement deposition

    • phagocytosis

• Pore forming beta-hemolysin/cytolysin

---

Risk groups based on age

• Neonates less than 1 month old

  • vertical transmission: mother to infant

• Infants from 1-23 months old

• Adults >60 

  • Underlying risk factors: diabetes mellitus, malignancy

Streptococcus agalactiae

Describe the different hemolytic presentation on agar

Describe CSF Analysis

• Procedure

• What is the normal CSF cell count

• What can cause an abnormal CSF cell count

• What is the normal glucose levels?

  • These measurements determine?

  • What can cause abnormal Glucose levels?

• What is the normal protein levels?

  • What can cause elevated levels?

  • What diseases can it indicate

• Describe microbial analysis

  • Types

  • Procedures

Procedure:

• Specimen collection

  • Up to 4 samples collected

• 2-3 mL each

• Each sample is labeled based on order of draw

  • Tube #1 – chemistry/serology

  • Tube #2 – microbiology

  • Tube #3 – hematology

  • Tube #4 – special immunologic tests, protein electrophoresis

---

CSF cell counts

• Normal – no cells

  • 0-5 wbc/uL

• Differential

  • Obtained via cytospin prep

  • Tube #3 – hematology = specimen of choice

---

CSF Cell Counts abnormal:

• Neutrophilia

• Bacterial meningitis

• Tubercular meningitis

• Fungal meningitis

• Increased lymphocytes

  • Viral meningitis 

---

Glucose

• 60% of the blood glucose level

• Measurement is useful to determine

  • Impaired transport of glucose from plasma to CSF

  • Utilization by leukocytes and microbes

• Abnormal Glucose Determinates 

  • Increased WBC w/ predominant neutrophils + decreased CSF glucose 

    • bacterial meningitis

  • Increased WBC w/ predominant lymphocytes + decreased CSF glucose 

    • tubercular meningitis

  • Increased WBC w/ predominant lymphocytes + normal CSF glucose 

    • viral meningitis

---

Protein:

• Normal: 15-45 mg/dL

Usage of Protein Levels:

• Nonspecific indicator of some type of degenerative process

  • Meningitis, brain abscess, MS

• Elevated Levels ->

  • increased permeability of BBB

  • Increased immunoglobulins in CNS

  • Decreased clearance of normal protein from CSF

  • Degeneration of neuronal tissue

  • Traumatic tap

---

Microbial analysis

• Types:

  • Gram stain, 

  • Acid-fast stain, 

  • fluorescent antibody stains

• Procedure:

  • CSF Centrifuged

  • Slide or cytospin prep, and cultures are prepared

  • blood cultures

  • India Ink

    • detect fungal meningitis