Lecture 1: Meningitis GAS Pharyngitis Flashcards
3 YO girl w hx of ear pain, listless, and febrile.
Sx: ear pain, headache, sore neck, vomited twice and photophobic
In the absence focal neurologic symptoms a lumbar
puncture is done for CSF analysis. Antibiotics and
dexamethasone are initiated together. The CSF shows the
following:
– WBC 3000 cells/μL, protein 750 mg/dL, glucose 10 mg/dL
– Gram stain shows gram positive cocci in pairs
- Dx: pneumococcal meningitis as a complication of otitis media
- 3 most common causes of bacterial meningitis are encapsulated organisms
- Streptococcus pneumoniae (gram positive (gm +) diplococci)
- Haemophilus influenzae Type B (gm – coccobacillus)
- Neisseria meningitidis (gm – diplococcus
- GBS
- L. monocytogenes
Bacterial meningitis: Risk factors
Functional or anatomic asplenia
- Sickle cell disease and other hemoglobinopathies
- Congenital or acquired asplenia or splenic dysfunction
Chronic immunodeficiencies
• HIV
• Nephrotic syndrome and other chronic renal problems
• Lymphoma, leukemia and immune deficiencies caused by
their treatment. Solid organ transplantation
• Congenital immunodeficiencies
– Compliment pathway (C1, C2, C3, C4) deficiencies
– B-cell or T-cell lymphocyte deficiencies
• Hypogammaglobulinemia
Immunocompetent children
• Chronic heart disease
• Chronic lung disease
• CSF leak
• Cochlear implant
• Diabetes
Associations with specific bacteria
• terminal compliment pathway - meningococcus
• cochlear implant, CSF leak – pneumococcus
• Absence of opsonizing antibody - pneumococcus, H. influenzae
• Corticosteroid use (high dose) Listeria, Cryptococcus
• HIV – pneumococcus, Cryptococcus, Listeria
Bacterial meningitis: Med History
- Exposure to an individual with meningococcal or H. influenzae Type B infection
- Recent otitis media or respiratory infection(pneumococcus and H. influenzae)
- Injection drug use (Staphylococcus aureus)
- Otorrhea or rhinorrhea
- Recent travel to meningitis belt Northern sub Saharan Africa (meningococcus)
Bacterial meningitis: Mechanism of entry
• Neisseria meningitidis: oropharyngeal colonization with pathogenic strain
• Streptococcus pneumoniae: nasopharynx, (children) direct
extension across skull fracture, spread from contiguous (otitis
media) or distant site (pneumonia) (children and adults)
• Haemophilus influenzae: nasopharynx, (children) spread from contiguous or distant site (children and adults)
• Listeria monocytogenes across placenta or food borne. Occurs in neonates and elderly, HIV, pregnant women
• Coagulase negative Staphylococci: foreign body (CSF shunt)
• Staphylococcus aureus: foreign body, spread from bacteremic source (IVDU, skin, endocarditis), contiguous source (epidural abscess)
Bacterial meningitis: pathogenesis
Bacterial cell wall components (both living and dead
bacteria) initiate inflammatory response and cytokine
production.
– Peptidoglycan of pneumococcus and liposaccharides of
meningococcus and Haemophilus influenzae
– Break down of blood brain barrier results in vasogenic edema,
swelling, increased intracranial pressure.
– Cytotoxic and ischemic injury to brain cells
– Leads to neurologic complications of meningitis
» Confusion, seizures, cranial nerve palsies (motor and sensory)
cognitive deficits
Bacterial meningitis: Etiologies
Neonates: E. coli and Group B streptococci, Listeria
– Children over 1 month: Pneumococcus, meningococcus, Group B streptococci. (H. influenzae type B has almost disappeared since vaccine developed to Type B disease)
– Adults: Pneumococcus, meningococcus, Staph aureus.
Frequency depends on underlying risk factors.
Occasionally see H. influenzae non typable
• Listeria monocytogenes in pregnant women and elderly
Meningitis DDx
Viral meningitis
• More gradual onset
• CSF lower protein, higher glucose, fewer cells, more
lymphocytes
• PCR techniques can identify in hours to a day on CSF
specimens (enteroviruses, HSV-2 and HSV-1)
– Fungal meningitis
• Cryptococcus neoformans most common. Look for
immunosuppression. Gradual not acute onset
– TB meningitis
• Especially in young children, reactivation disease in adults
– Encephalitis
• Consider viral origins
• Seasonality to West Nile virus
• HSV-1 high mortality, morbidity. Treatable with IV acyclovir
Bacterial meningitis: management
- Outcomes worse with more advanced presentation and delay in treatment. If you think meningitis initiate investigations and therapy immediately!!!!
- Penicillin, third generation cephalosporin and/or vancomycin all given IV in high dose
- Mechanism of resistance to penicillin for pneumococcus is a change in penicillin binding protein (PBP) affinity not a beta lactamase (H. influenzae) or substituted PBP (MRSA)
17 yo w sore throat; no cough or rhinorrhea
- Predominant species for streptococcal pharyngitis is
- S. pyogenes (Group A streptococcus or GAS)
- Group C and Group G strep may also be causes.
- Grouping is based on acid extractable cell wall carbohydrate antigens (Lancefield grouping)
Multiple other causes of pharyngitis
- Beta hemolytic strep 15% of causes
- Viruses 50% of causes (Rhinovirus, Adenovirus, influenza A and B, Epstein Barr virus, Cytomegalovirus, HIV,
- Coxsackievirus, RSV, Metapneumovirus, Coronavirus)
- 30% no diagnosis
GAS pharyngitis sequelae
While GAS pharyngitis is short lived (2 to 5 days) the sequelae without antibiotics can be significant
– Poststreptococcal glomerulonephritis (PSGN),
– Rheumatic fever
– Toxic shock syndrome
– PANDAS (Paediatric Autoimmune Neuropsychiatric
Disorder associated with group A Streptococcus)
– Local and distant site suppurative infection
GAS pharyngitis may be accompanied by a rash and the findings referred to as scarlet fever
Streptococcal pharyngitis: Virulence factors
- Capsule in some strains (decreased phagocytosis)
- Lipoteichoic acid in peptidoglycan cell wall (adhesion)
- M-protein (inhibits antibody binding and compliment related opsinization)
- Fibronectin binding protein (adhesion)
- Vimectin (muscle adhesion)
- Streptolysin O (hemolysis on blood agar. Titers high and
help with diagnosis of PSGN and rheumatic fever) - Hyaluronidase (skin, deep tissue spread)
- Streptokinase (binds plasminogen → plasmin → fibrin →
fibrin degradation products) - Streptococcal pyrogenic exotoxins (SPE) A,B and C toxins.
(fever, rash of scarlet fever, streptococcal toxic shock
syndrome toxin. May also function as superantigens and
induce cytokine production.)
Complications of GAS: PSGN
- Risk greatest children 5 to 12 and adults > 60
- Can occur following pharyngitis or skin infection (5 to 10% attack rate from pharyngitis and 25% from skin infection in one epidemic). Can also be sporadic
- Related to circulating strain virulence factors (SPEB)
Complications of GAS: Scarlet fever
- Diffuse rash in association with pharyngitis
- Starts in head and neck. Circumoral pallor and strawberry tongue also found. Rash is raised and has sandpaper like appearance
- Rash spreads to torso and then limbs
- Eventually desquamates
Complications of GAS: Local suppurative extension
Peritonsilar abscess
– Can extend into deep spaces of neck
– Other organisms can become involved (Fusobacterium
necrophorum) Anaerobe resistant to azithromycin. (azithromycin
is used for sore throat penicillin allergic patients) Leads to septic
thrombosis of jugular vein and septic pulmonary emboli to lungs
causing lung abscess
– Require surgical drainage of neck abscess
Otitis media
– Extension to middle ear via Eustachian tube
– Less than 10% of causes of otitis media
– Otalgia, fever, irritability
Necrotising fasciitis
Strep pharyngitis: Investigations
- Throat swab is the gold standard test
– Not possible on clinical grounds to differentiate
between bacterial and viral pharyngitis
– Can also do rapid antigen detection testing
– ASOT (antistreptolysin O titer) can be used to
confirm prior GAS infection in patients with glomerulonephritis or acute rheumatic fever.
Greater than 200 Todd units is positive
