Group A Streptococcal Diseases (cont.)

Nonsuppurative Sequelae

Post-infection complications of Group A streptococcal disease; Serious complications in pre-antibiotic era; still important in developing countries

Acute rheumatic fever (ARF):

Inflammation of heart, joints, blood vessels, sub- cutaneous tissues

Rheumatic heart disease (RHD):

Chronic, progressive heart valve damage

Acute glomerulonephritis (AG):

Acute inflammation of renal (kidney) glomeruli

Foodborne Disease

Epidemiology of Acute Streptococcal Infection

• Predilection for upper respiratory tract or skin

•Group A commonly colonize oropharynx of healthy children

•M-types of strains colonizing throat differ from those on skin

•Rapidly killed after phagocytosis, but cell walls not digested and may lead to chronic inflammatory lesions

Pharyngitis transmitted by droplets from respiratory secretions

• Crowding increases risk (e.g., classrooms, day care facilities)

Pyoderma transmitted by direct contact with infectious lesions

Nonsuppurative Sequelae of Acute Group A Streptococcal Infection

Acute Rheumatic Fever (ARF)

Inflammatory reaction characterized by arthritis, carditis, chorea (disorder of CNS with involuntary spastic movements), erythema marginatum (skin redness with defined margin), or subcutaneous nodules

Within 2-3 weeks following pharyngitis

•Epidemic pharyngitis: ARF in as many as 3%

•Sporadic pharyngitis: ARF in 1 per 1000

Morbidity & mortality linked to subsequent disease of heart valve

(Rheumatic Heart Disease)

Poorly understood pathogenesis with several proposed theories including cross-reactivity of heart tissues & strep AGNs

•?? (Type II hypersensitivity, exotoxins, direct invasion)

Nonsuppurative Sequelae of Acute Group A Streptococcal Infection (cont.)

Acute Glomerulonephritis

Follows either respiratory (pharyngitis) or cutaneous (pyoderma) streptococcal infection

Associated with well-defined group of M-types Incidence varies from <1% to 10-15%

Most often seen in children manifesting as dark, smoky urine with RBC's, RBC casts, white blood cells, depressed serum complement, decreased glomerular filtration rate

Latent period: 1-2 weeks after skin infection and 2-3 weeks after pharyngitis

Granular accumulations of immunoglobulin due to deposition of immune complexes within the kidney

(Type III Hypersensitivity)

Determinants of Pathogenicity

Cellular Virulence Factors

Capsule

Antiphagocytic; Nonspecific adherence

Hyaluronic acid (polysaccharide) mimics animal tissue

Lipoteichoic Acid

Cytotoxic for wide variety of cells

Adherence: Complexes with M protein (LTA-M) and binds to fibronectin on epithelial cells

M-Protein

LTA-M protein is adhesin

Antiphagocytic

Inhibits alternate C’ pathway and opsonization

M-like Proteins: bind IgM and IgG

F Protein: mediates adherence

Extracellular Virulence Factors

Exotoxins:

Streptolysin O (SLO):

Hemolytic and Cytolytic

Prototype of oxygen-labile and thiol-activated cytolytic exotoxins (e.g., Streptococcus, Bacillus, Clostridium, Listeria)

Lytic for variety of cells: bind to cholesterol- containing membranes and form arc- or ring- shaped oligomers that make cell leaky (RBC's, WBC’s, PMN's, platelets, etc.)

Causes sub-surface hemolysis on BAP Stimulate release of lysosomal enzymes

SLO titer indicates recent infection (300-500 in pediatric populations)

Extracellellular Virulence Factors (cont.)

Exotoxins (cont.):

Streptolysin S (SLS):

Hemolytic and Cytolytic Oxygen stable, non-antigenic

Lytic for red and white blood cells and wall-less forms (protoplast, L- forms)

Causes surface hemolysis on BAP

Lysogeny: Lysogenized bacteriophages play key role in directing synthesis of various Group A streptococcal enzymes and toxins

•Pyrogenic Exotoxin (erythrogenic toxin)

•Phage-associated muralysins (lyse cell walls) produced by both Groups A and C

Extracellular Virulence Factors (cont.)

Enzymes:

Nucleases: Four antigenic types (A,B,C,D)

Facilitate liquefication of pus generating growth substrates Nucleases A, C have DNase activity

Nucleases B, D also have RNase activity

Streptokinases: Two different forms

Lyse blood clots: catalyze conversion of plasminogen to plasmin, leading to digestion of fibrin

C5a Peptidase: destroys C’ chemotactic signals (C5a) Hyaluronidase: hydrolyzes hyaluronic acid

Others: Proteinase, NADase, ATPase, phosphatase, etc.