• Epidemiology
  1. In 2022, there is an increase globally of invasive Group A Streptococcus and Scarlet Fever
    1. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON429
  2. Group A Streptococcus results in 700 million infections and complicated by 500,000 deaths each year worldwide
    1. Carapetis (2005) Lancet Infect Dis 5(11): 685-94 [PubMed]
  3. Post-streptococcal complications have become uncommon in the United States
    1. Complications are more common in Sub-Sahara Africa, India, Australia, New Zealand
  • Pathophysiology
  • General
  1. Anaerobic Gram Positive Cocci
    1. Beta-hemolytic Streptococcus (induces complete RBC Hemolysis in its vicinity)
    2. Lancefield Group A (C CarbohydrateAntigen) in Bacterial cell wall
    3. Pyogenes is derived from greek "pus forming"
  2. Humans are only reservoir
  3. Beta Hemolysis Factors
    1. Streptolysin O
      1. Inactivated by oxygen (oxygen labile)
      2. Lyses WBC and RBC (causing beta-Hemolysis)
      3. Measurable with acute infection (ASO Titer)
    2. Streptolysin S
      1. Oxygen Stable
      2. Also contributes to beta hemolytic activity
  4. Virulence Factors
    1. Hyaluronidase
    2. Anti-C5a Peptidase
    3. DNAase
    4. Streptokinase
      1. Activates plasmin, triggering Fibrinolysis (nearly identical to staphylokinase)
      2. Streptokinase is extracted from Group C Strep to be used in MI and Stroke (prior to tPA, TNK)
    5. Lipoteichoic Acid
      1. Aids in Bacterial adherence
    6. M Protein
      1. Inhibits Complement Activation
      2. Inhibits Phagocytosis, and allows for rapid subcutaneous spread (e.g. Necrotizing Fasciitis)
      3. M Protein also provides an Antigenic target for immune response to clear infection
  5. Toxins
    1. Pyrogenic exotoxin (erythrogenic toxin)
      1. Expressed by strains that cause Scarlet Fever
    2. Toxic Shock Syndrome Toxin (TSST)
      1. Exotoxins hyperstimulate T-Cell response with high Cytokine release (Toxic Shock Syndrome)
      2. Similar to Staphylococcal exotoxin
  6. Antibiotic management of Streptococcal Pharyngitis and decreases Rheumatic Fever risk
    1. However, does not prevent Post-Streptococcal Glomerulonephritis
  7. Autoimmune complications arise from Antibody formation against streptococcal M Protein
    1. Immune complex deposition in Post-Streptococcal Glomerulonephritis
    2. Antibody directed reaction in Acute Rheumatic Fever
    3. Autoantibody cross-reaction to Basal Ganglia in Sydenham Chorea