Biology 216 Lecture
Streptococcus pneumoniae
A. Bacteriology - Major cause of pneumonia, 
		meningitis, otitis media
	1. Basics - Gm+ cocci, usually diplococci, lancet shaped.
	Also referred to as pneumococcus 
		(old name Diplococcus pneumoniae) 
	Alpha hemolytic (confused with 
		viridans streptococci); CO2 growth
  	2. Products
	- Polysaccharide capsule - protective Ag; 
		lost in lab transfer.
	84 serotypes of capsule (vaccine to 23 which account 
		for 87 % of disease)
	- IgAase (by most virulent strains) - Often with 
		mucosal organisms
	- Pneumolysin - RBC lysis. Putative virulence factor 
		(binds cholesterol)
B. Pathogenesis
	1. Carried by 15 % of adults (higher in institutions)
	Higher carriage -> higher incidence 
		(boarding schools, military...)
	Attachment to URT epithelia
	2. Disease - endogenous in most cases 
		(30 %transient carriage)
	Otitis media (eustachian tube), pneumonia, 
		bacteremia, meningitis.
	Invasion - to lung or blood of compromised host
	Compromised hosts - Vaccine candidates
		Decreased ciliary clearance 
			(chilling, anaesthesia, unconscious,
		       	smoking, alcohol, vira)
		Immunocompromised
		Spleen dysfunction- Important filtration/
			clearing organ.
		Splenectomy
		Sickle cell (spleen shot, so can't clear)
		Contact new serotype.
	Initiation of SEVERE inflammation reaction 
		(from cell wall materials, PG, teichoic) 
		-> IL-1, TNF, C-activation-> edema, endothelial damage.....
C. Clinical Manifestation: CDC estimates (not reportable)

Manifestation	Cases/yr (US)	Case Fatality (w/treatment)
Pneumonia	150,000 - 570,000	5 %
Bacteremia	16,000 - 55,000	20 %
Meningitis	2,000 - 6,000	30 %

	1. Pneumonia - accounts for 90 % of bacterial pneumonia
	Most cases - elderly, young, AIDS
    	Lobar pneumonia (entire lobe fills with pus
		 - may be multi lobe - 5 possible)
	Primarily in elderly and age 1 -2 years.
    	Three stages - 
		a. Edema (inflammation, outpouring fluid, few PMN
		b. Consolidation - Visible on x-ray; 
			PMN/RBC exudate
		     Phagocytosis - crowding 
			(surface phago; opsonic)
		     Severe inflammation -> 
			cyanosis, bloody sputum
		c. Resolution - Macs clean up; x-ray clears
	Symptoms - Acute sudden onset; chill, fever, 
		productive cough, chest pain,
		bloody sputum, weak; Crisis in 1 week 
		or soon after antibiotics.
	2. Bacteremia - Hematogenous spread
		 (joints, heart valve, mening
	3. Meningitis - Major cause of adult meningitis 
		(blood or direct extension ear)
	     Severe: convulsions, headache, fever, nausea, 
		neurosequelae - retard, deaf
	4. Otitis media - middle ear through eustatian tube.
D. Diagnosis
	1. X-ray
	2. Gm+ diplococci in sputa (clean sample with 
		few epithelial cells, many PMN)
	3. Isolation and ID
	     Specimen - sputum, transtrachial aspirate 
		(unconscious patient), blood, CSF
	 Growth - BAP, CO2
	ID - alpha hemolytic (differentiate from viridan strept)
	    bile solubility (activates NAM-ala amidase 
		-> autolysis) - 10 min clearing
	    optochin sensitivity (activates autolysins)
	4. Antigen detection - CIE
	5. DNA hybridization test for immediate ID
E. Treatment - rapidly fatal so treat immediately; 
		penicillin (97 % sensitive)
	Gradual resistance to Pen and Tet over years.
	30 % mortality in infants with penicillin alone 
	     (releases cell wall parts which enhance
		 inflammation in brain
		-> increase intracranial pressure)
	Current - B-lactam + dexamethasone (SAID)
		 -> 5 % mortality
F. Prevention - Vaccine
    1918 - first vaccine (killed bacteria)
    1977 - First polysaccharide capsule vaccine 
	(12 serotypes) - no effect at mucosa
    1983 - 23 serotypes (covers 87 % of disease)
	 - single dose of 25 ug.
    Population 
	- COPD (chronic obstructive pulmonary disease patients)
		Asthma, emphysema, smokers, 
	- Alcoholic, sickle cell, miners 
		(study group for 23 valent vaccine)
            - elderly (>65 yr old) - suggested given with flu vaccine.
	- not < 2 year old (poor immune response)
	- prior to immunosuppressive therapy 
		(transplant, splenectomy)
     Side effects: polyneuritis (mild) - numbness
    2001 - heptavalent capsule-protein conjugate childhood vaccine.