GROUP A STREPTOCOCCI
I. GENERAL COMMENTS
II. STRUCTURE AND PHYSIOLOGY
III. GP A STREPTOCOCCAL DISEASE
A. PRIMARY DISEASES
1. SEPTIC SORE THROAT AND SCARLET FEVER
2. SKIN AND TISSUES
3. FEMALE GENITAL TRACT
4. DISSEMINATED DISEASE
5. TOXIC SHOCK-LIKE DISEASE
6. INVASIVE GROUP A STREP
B. LATE SEQUELAE: ARF & AGN
V. IMMUNITY TO REINFECTION
VI. LABORATORY DIAGNOSIS
VII. TREATMENT
VIII. PREVENTION AND CONTROL
GROUP A STREPTOCOCCI
(STREPTOCOCCUS PYOGENES)
I. General Comments:
A. Cause wide variety of disease in humans and animals: suppurative and nonsuppurative
B. 21 gps of streps (based on (except for viridans) antigenic diversity of cell wall CHO and over 85 serotypes of a single species - S.pneumoniae
C. Gp A and S. pneumoniae responsible for most human disease: In US 10,000,000 cases/yr. GpA strep throat 500,000 cases/yr. S. pneumoniae pneumonia
D. Gp A strep important cause of pharyngitis, scarlet fever, erysipelas, impetigo
E. RECENT IMPT DISEASE
Systemic GpA streptococcal toxic shock-like syndrome associated with erythrogenic (scarlet fever) toxin A production -->severe systemic manifestations with case fatality ratio of up to 30%
II. Structure and Physiology
A. Microscopic morphology:
Gm +, nonmotile cocci occurring in short or long chains, occasionally singly and in pairs.
Fresh isolates are encapsulated but capsules are lost rapidly during in vitro cultivation.
B. Physiology:
Complex nutritional requirements (satisfy by adding blood to growth medium). Grow best with increased carbon dioxide on blood agar at 37C
Ferment carbohydrates with production of lactic acid
Depending on group exhibit either alpha, beta, or gamma hemolysis.
Gp A exhibits beta hemolysis
Hemolytic properties important in preliminary identification of isolates.
C. Antigenic Structure of GpA streptococci (relating to classification and/or virulence) (Figure 1)
1. "C" carbohydrates: cell wall polysaccharides; basis for classification into 20 serological groups (A - V; I & J omitted)
These Gp specific Ags are covalently linked to peptidoglycan
2. Lipoteichoic Acid (LTA): Surface exposed molecule; covalently linked to cytoplasmic membrane glycolipid.
Extends through the cell wall and capsule
In concert with M protein - LTA mediated attachment to oral and skin surface and subsequent colonization
Mechanism thought to involve fibrillar network created by ionic interaction between negatively charged LTA and positively charged M protein.
3. M proteins: Surface-exposed "fuzz" dimeric molecules ranging in MW from 40K to 80K
Anchored to cytoplasmic membrane at carboxy terminus and extend through the cell wall and capsule as a fibrillar structure (two alpha helical chains twisted about each other
M PROTEIN IS CONSIDERED TO BE THE MAJOR VIRULENCE FACTOR OF GP A STREPS
Anti-phagocytic activity in absence of specific antibody and complement by blocking deposition of C3b
Mediator of attachment in concert with LTA
Antibody to M protein protective
Cross-reactivity of anti-M protein Ab with human cardiac tissue raises questions about vaccination with whole M protein
4. Capsule: hyaluronic acid (indistinguishable from tissue ground substance) ; anti-phagocytic activity
5. Fc receptors: bind Fc domain of mammalian immunoglobulin; role in virulence by virtue of anti-phagocytic mechanisms
6. C5a peptidase: Surface bound endopeptidase; cleaves C5a component of complement; Inhibits ability of C5a to act as chemoattractant for PMN
7. Streptolysin S (S=stable) Lyses human RBCs and phagocytic cells by direct cell-to-cell contact; largely cell membrane bound and oxygen stable; antigenic
D. Extracellular products associated with or thought to be associated with pathogenicity:
1. Streptolysin O: (O=oxygen labile); produced by most GpA streps; Immunogenic protein, Lyses RBCs and damages PMNs by binding to membrane sterols and producing holes in membrane --> causes release of lysosomal enzymes and degranulation
Able to destroy adjacent cells and tissues and contributes to spread of the organism form local sites
Measure anti-streptolysin O Ab to determine recent GpA streptococcal disease
2. Pyrogenic (erythrogenic) Exotoxins: responsible for rash of scarlet fever; toxin coded for by bacteriophage and produced by strains lysogenic for the phage
3. Dnases: contributes to spread; depolymerizes DNA in thick pus as result of PMN disintegration
4. Hyaluronidase: Hydrolyzes hyaluronic acid; facilitates spread of organism through tissues; produced by most strains
5. Streptokinases(fibrinolysins): Converts plasminogen to plasmin - leading to fibrin digestion; facilitates spread of organism from local sites
III. Gp A Streptococcal Disease
A. Habitat
Restricted to humans (some evidence of pet carriage (GI tract)
Major habitats: Nose, throat, and skin of 5 - 15% of humans
Also found in vaginal tract
B. Transmission:
EXOGENOUS: Droplet nuclei from case or carrier to respiratory tract
Contaminated instruments
Droplet nuclei into wounds, burns, abrasions
Ingestion of milk contaminated by case or carrier
ENDOGENOUS: Activation from nose, throat, skin of carrier to areas of impaired host resistance
Defects in host resistance caused by: viral disease, congenitally damaged heart valves, wounds, burns, or abrasions
Not known: What determines whether an individual will become colonized(carrier), clear the organism, of develop disease following exposure
Mechanisms that influence maintenance of the carrier state vs "activation" and resulting endogenous disease
IV. Primary Diseases of Mucous Membrane Surfaces, Skin, and/or Subcutaneous Tissues
A. Septic sore throat and Scarlet Fever:
1. Occur in all age groups but most often in young children
2. Initiated by droplet nuclei from case or carrier into a susceptible host or endogenously by factors that upset host-parasite equilibrium
3. Organisms attach to pharyngeal mucosa through LTA ligands (in concert with M protein) and colonize
4. M protein major factor in preventing phagocytosis by PMNs but capsule also contributes
5. C5a peptidase may play role by reducing number of incoming PMNs
6. Many PMNs destroyed by leukotoxic activity of Streptolysin S and elaboration of Streptolysin O
7. Surviving PMNs able to phagocytize GpA streptococci
8. Septic sore throat end result of process and manifests as an acute, erythematous, pharyngitis and/or tonsillitis accompanied by grayish-yellow purulent exudate, cervical lymphadenitis and fever
9. If organism produces pyrogenic exotoxin, the end result is scarlet fever; SF occurs as a diffuse reddening of skin with rash most prominent on trunk, neck, and extremities
Organisms may spread from pharynx by direct extension to produce abscesses in
Sinuses
Middle ear
Mastoid
Meninges
Downward extension into the lungs --> pneumonia
Organisms may spread by hematogenous route from any primary disease sites with resultant septicemia, acute endocarditis, purulent joint involvement, and multiple organ abscesses
B. Skin and Subcutaneous Tissues Involving Wounds, Burns, and Abrasions
1. Diseases listed below characterized by abscesses by same mechanism as described for septic sore throat
2. Impetigo: these strains may cause acute glomerulonephritis
3. Erysipelas: End result is disease of skin and subcutaneous tissues usually occurring on face of lower extremities and characterized by fiery red, advancing erythema
4. Cellulitis, Lymphangitis, and Lymphadenitis: Occur in all age groups; organisms travel along lymphatic channels from cell to cell resulting in purulent inflammation of skin and subcutaneous tissues
C. Primary disease of the female genital tract
Puerperal sepsis: disease of uterine endometrium, initiated during or after delivery of newborn by droplet from case or carrier, by contaminated instruments, or endogenous activation in pharyngeal or vaginal carriers.
D. Disseminated Disease
Late Sequelae
Often occurs
High case fatality rate when dissemination occurs
Streptolysin O
Dnases
Hyaluronidase All may contribute to spread
Streptokinases
E. Severe systemic shock-like disease associated with GpA streps producing pyrogenic exotoxin A
Characterized by a scarlet fever-like rash, respiratory distress, myositis, shock, and relatively high case fatality rate.
F. Invasive Gp A Strep infections
1. Specific strains involved (m-1 and M-3 serotypes)
2. Predisposing factors: wounds (surgical or non-surgical), diabetes, other underlying problems
3. Life-threatening infection: organism penetrates mucous membrane or colonizes a skin lesion (can even be a bruise)
a. Can lead to necrotizing fasciitis - inflammation and destruction of the sheath that covers the skeletal muscles.
b. OR to myositis: the inflammation and destruction of skeletal muscle and fat tissue
This can happen very quickly - “Galloping gangrene”
4. 85% of invasive strains carry genes for production of streptococcal pyrogenic exotoxins A and B (Spe exotoxins)
Exotoxin A: a super antigen - stimulates production of abnormally large quantities of cytokines. They damage the endothelial cells lining the blood vessels, causing fluid loss and rapid tissue death from lack of oxygen
Exotoxin B: a cystein protease. rapidly destroys tissue by breaking down proteins.
G. Late Sequelae: Nonsuppurative Diseases ARF and AGN
1. Acute Rheumatic Fever: Can occur when preceded by pharyngitis
Hypothesis is cross-reactive epitopes among M proteins and target tissues including cardiac tissue, and binding of anti-M protein antibody to tissue epitopes.
Major clinical manifestations are carditis, polyarthritis, and subcutaneous nodules
2. Acute Glomerulonephritis: Occurs most commonly in children
Can result when preceded by pharyngitis or skin disease (especially impetigo)
Evidence supports concept that renal damage is result of immune complex deposition on the glomerular basement membrane and complement activation that generates a massive inflammatory response, membrane damage, and intravascular coagulation
Major clinical manifestations are renal glomerular damage, hypertension, edema, proteinuria, and hematuria
V. Immunity to Reinfection
A. Immunity to septic sore throat reinfection is serotype specific
B. Immunity to scarlet fever reinfection only to specific exotoxin that caused rash
C. Skin and puerperal sepsis disease, serotype-specific antibody minimal; immunity to reinfection does not occur
D. Recurrences of RF are frequent; any of the >80 serotypes can initiate the preceding pharyngitis
E. Recurrences of AGN rare due to limited number of nephritogenic strains
VI. Laboratory Diagnosis
Clinical appearance (e.g. impetigo) usually start antibiotic before culture id complete
Strep throat - culture and ID
Latex bead agglutination (e.g. Streptex for grouping)
VII. Treatment
Adequate drainage, debridement, antibiotic therapy essential for treatment of localized, suppurative skin lesions
Penicillin drug of choice for acute disease
Penicillin has no effect upon established rheumatic heart disease and AGN
Resistant strains have not been reported
Erythromycin drug of choice in allergic individuals
Rapid eradication of organism essential to prevent or reduce occurrence of late sequelae
VIII. Prevention and Control
A. Penicillin effective in elimination of cases and carriers during community outbreaks
B. Adherence to aseptic techniques in hospital environments
C. Prophylactic penicillin therapy recommended form prevention of recurrent rheumatic fever: prior to dental, genitourinary, and GI manipulations
D. No vaccines yet: M protein vaccine a problem because of cross reaction with shared epitopes
