Streptococcus pyogenes (Group A Streptococcus, GAS)

Morphology and culture

• It is a Gram-positive coccus that is spherical or ovoid and arranged in chains. The cocci divide in a plane perpendicular to the chain axis. Old or dying cultures can stain Gram-negative. (Jawetz Melnick & Adelbergs Medical Microbiology 28e, p. 222)
• Most strains have a hyaluronic acid capsule, which is antiphagocytic. It is most obvious in young cultures. (Jawetz 28e, p. 222)
• It grows poorly unless the medium is enriched with blood or tissue fluids. Growth and hemolysis improve in 10% CO2, and the optimum temperature is 37°C. (Jawetz 28e, p. 222)
• On blood agar the colonies are small and surrounded by a sharp zone of β-hemolysis. (Jawetz 28e, p. 223)
• It is PYR-positive and usually bacitracin-sensitive. (Jawetz 28e, p. 222)
• Matte colonies make a lot of M protein and are virulent. Glossy colonies make little M protein and are usually avirulent. (Jawetz 28e, p. 223)
• β-hemolysis comes from streptolysin S (oxygen-stable) and streptolysin O (oxygen-labile). Strains lacking streptolysin S are β-hemolytic only anaerobically. Such strains are missed if plates are incubated only aerobically. (Sherris & Ryan's Medical Microbiology 8e, p. 1000-1001)

Antigenic structure

• Cell wall: the group-specific C carbohydrate is the basis of Lancefield grouping. The wall also contains the proteins M, T and R, and peptidoglycan.
• M protein is the major virulence factor. (Jawetz 28e, p. 223)
  • It is a filamentous, coiled-coil molecule projecting from the cell wall.
  • It resists phagocytosis by inhibiting activation of the alternative complement pathway.
  • There are more than 100 to 150 M types. Immunity is type-specific, so repeat infections with different M types are possible.
  • Class I M protein cross-reacts with cardiac muscle and is linked to rheumatic fever.
• Other adhesins: lipoteichoic acid and protein F bind fibronectin on epithelial cells. (Sherris 8e, p. 1001-1002)

Toxins and enzymes (Jawetz 28e, p. 223-224)

Diseases (Jawetz 28e, p. 224-226)

• Erysipelas: raised, red lesion with a sharply demarcated, rapidly advancing edge.
• Cellulitis: not raised, with an indistinct border.
• Necrotizing fasciitis ("streptococcal gangrene").
• Puerperal fever.
• Bacteremia and sepsis.
• Streptococcal toxic shock syndrome: mainly M types 1 and 3, SpeA-producing strains.

• Pharyngitis is the commonest. It presents with tonsillitis, purulent exudate, tender cervical nodes and high fever, and about 20% of infections are asymptomatic.
• Scarlet fever: pharyngitis plus an erythrogenic toxin rash.
• Pyoderma (impetigo): superficial vesicles that become pustular and crusted. It is highly communicable in hot, humid climates.

• Acute glomerulonephritis
  • It follows pharyngitis or skin infection.
  • It is caused by immune complexes (SpeB and a nephritis-associated plasmin receptor).
  • Findings are hematuria, proteinuria, edema, hypertension and low complement.
  • Penicillin does not reverse it. Prophylaxis is not used because few nephritogenic types exist.
• Acute rheumatic fever (ARF)
  • It follows pharyngitis (not skin infection) by 1 to 5 weeks, with a mean of 19 days.
  • It comes from molecular mimicry, with cross-reaction to heart tissue.
  • Features are fever, migratory polyarthritis, carditis (with Aschoff bodies in the myocardium), and Sydenham's chorea.
  • It tends to recur with repeated streptococcal infection, and cardiac damage worsens with each attack.
  • The M types most often involved are 1, 3, 5, 6 and 18.
• PANDAS is a proposed post-streptococcal neuropsychiatric disorder, and the link is not firmly established.

Laboratory diagnosis (Jawetz 28e, p. 226)

• Specimens: throat swab, pus, blood, CSF or other sterile fluid, and serum for antibodies.
• Smear: Gram stain of a throat swab is rarely useful because viridans streptococci look identical.
• Culture: blood agar, with stab inoculation or CO2 to enhance hemolysis.
• Identification: PYR test, Lancefield group A antigen detection, and bacitracin sensitivity (presumptive only).
• Rapid antigen detection test (RADT): 60 to 90% sensitive and 98 to 99% specific. Nucleic acid amplification tests are more sensitive but cost more.
• Serology: ASO is most useful after respiratory infection. Anti-DNase B and anti-hyaluronidase are best after skin infection. A high ASO titer (>250 units) suggests recent or repeated infection and is commoner in rheumatic patients. The titers show infection, not immunity.

Treatment and prevention (Jawetz 28e, p. 226-227)

• Treatment: all strains remain uniformly sensitive to penicillin G. Give a 10-day course so that the antigenic stimulus is eliminated before about day 8, which prevents sequelae.
• Penicillin allergy: macrolides or clindamycin, but macrolide resistance is rising.
• Antibiotics do not affect established glomerulonephritis or ARF.
• Secondary prophylaxis after ARF: benzathine penicillin G IM every 3 to 4 weeks, or daily oral penicillin or a sulfonamide. It is continued for years.
• Control: treat the human source early. Droplets and nasal discharge from carriers and infected people are the main route of spread.

Recent evidence update

• One finds that S. pyogenes is often a passenger rather than a pathogen in uncomplicated sore throat (PMID 38762046).
• One covers antibiotics for eradicating pharyngeal carriage in asymptomatic people (PMID 38360357).
• One covers strain diversity and vaccine development (PMID 38070538).