what are some major characteristics of streptococcus?

• gram positive cocci in pairs or chains
• catalase-negative
• classification based on hemolytic pattern:
  • Beta: complete RBC lysis, resulting in clearing around colony
  • Alpha: incomplete RBC lysis, resulting in "greening" of agar around colony
  • Gamma: misnomer, actually an *absence* of RBC lysis around colony
    • alpha or gamma=viridans streptococci (more than 25 species, divided into 5 groups)
• serological classification is used to classify beta-hemolytic streptococci
  • divided into groups A-W based on unique cell wall carbohydrates
  • carbs detected by Abs
  • A, B, C, F, G= most common pathogens
  • knowledge of group can predict pathogenicity
• biochemical assays also used to define species; commonly used for viridans species

• suppurative= pus associated
• examples:
  • pharyngitis
  • skin and soft tissue infections

• rheumatic fever
• rheumatic heart disease
• acute glomerulonephritis

what is the most common and important member of group A beta-hemolytic streptococci?

what strep species are common viridans group members?

Streptococcus anginosus

Streptococcus mitus

what are some important cell wall proteins found in Strep pyogenes?

• M protein: type specific proteins with specific types associated with virulent strains
• M-associated proteins
• F (fibronectin-binding) proteins

**S. pyogenes is also surrounded by a polysaccharide capsule made of hyaluronic acid (identical to host connective tissue)**

what structural molecules are important in antiphagocytic activity of S.pyogenes?

• bacterial capsule: poor immunogen, interferes with phagocytosis
• M proteins: degrades C3b, an important mediator of phagocytosis
• C5a peptidase: inactivates C5a, a chemoattractant of neutrophils and mononuclear phagocytes
  

what structural molecules are important in helping S.pyogenes adhere to host cells?

• lipoteichoic acid: responsible for initial binding to host cells
• M proteins: adherence to specific receptors on host cell
• F proteins: adherence to specific receptors on host cell

what structural molecules are important in helping S.pyogenes invade host epithelial cells?

• M proteins
• F proteins

what role do streptococcal pyrogenic exotoxins (spes) play in pathogenicity of Streptococcus?

• SpeA, SpeB, SpeC, SpeF (all heat-labile toxins)
• superantigens that stimulate release of pro-inflammatory cytokines and hyperstimulate the immune reaction
• responsible for the clinical manifestationsnecrotizing fasciitis, toxic shock syndrome of severe streptococcal disease (ie: )
• also responsible for the rash assd with scarlet fever

what are some critical hydrolytic enzymes employed by Strep pyogenes?

• Streptolysins S and O
  • hemolysins capable of lysing RBCs, WBCs, and platelets
  • Abs made against Streptolysin O but NOT AGAINST streptolysin S
• Streptokinase
  • binds to plasminogen activator to make active plasmin that will degrade fibrin, a process which may be responsible for the rapid spread of group A streptococci in infected tissues
  • used in purified form to dissolve clots!
• DNAses A to D
  • dissolve nucleic acids released from lysed host cells, which prevents formation of a viscous matrix that inhibits bacterial spread
• anti-streptolysin O Abs, anti-streptokinase Abs, DNAse Abs can be measured to determine whether a previous infection with S. pyogenes has occurred
• C5a peptidase degrades C5a, an important chemoattractant that aids in phagocytosis activation

anti streptolysin O antibodies

no abs are made to streptolysin S

• molecular mimicry: anti-Strep Abs cross-react with cardiac tissue, particularly myosin and valvular proteins
• these Abs facilitate infiltration of T cells into heart tissue, production of inflammatory cytokines, leading to progression and maintenance of cardiac valve lesions
• RF is is a sequel of pharyngitis and of skin/soft tissue diseases

what is the pathogenic basis of acute glomerulonephritis ?

• pathogenesis not clearly understood
• evidence for deposition of immune complexes in kidney, and some molecular mimicry
• more likely theory:
  • particular nephritogenic strains of S.pyogenes produce Ags that activate enzymes that damage the glomerular basement membrane resulting in protein loss and a decrease in renal function
• acute glomerulonephritis is a sequel of pharyngitis and of skin/soft tissue diseases

oral secretions passed via hand to mouth ; infection contact with broken skin

• a GAS
• inflammation of the pharynx with exudates (any fluid that filters from blood into areas of infection or inflammation) and cervical lymphadenopathy
• GAS strains that secrete an endotoxin produce an erythematous rash over chest/extremities (scarlet fever)

localized skin infection (primarily on face, arms, legs)

infection of skin with lymph node involvement and evidence of systemic spread (fever, chills, leukocytes)

typically preceded by pharyngitis or localized skin infection

fluid filled vesicles that may be cultured for organisms

• streptococcal gangrene
• deep-seated infection that causes necrosis of subcutaneous tissues and muscle

• multisystem toxicity
• initially presents as localized soft tissue infection but rapidly progresses to shock, multiorgan failyre, systemic toxicity
• M serotypes 1,3 are most common
• "flesh eating bacteria" produce pyrogenic exotoxins A or C (speA, speC)

• useful: pyogenic infections of normally sterile sites
• not useful: pharyngitis (difficult to differentiate GAS from other streptococci in mouth), rheumatic fever, glomerulonephritis

both specific probe and amplification tests are available; generally as sensitive and specific as culture.

• many immunological tests have been developed to detect the group-specific carbohydrate in pharyngeal specimens
• "rapid strep tests"
• unproven value for other infections
• good specificity, low sensitivity

why is streptolysin O a useful test only for diagnosis of S.pyogenes infection in rheumatic fever?

• Abs against streptolysin O (ASO) develop 3-4 weeks after onset of pharyngitis; streptolysin O binds to skin lipids and does not stimulate an Ab response in pyogenic skin infections
• ASO test is reliable to diagnose S.pyogenes infection in patients w/ RF but not glomerulonephritis because:
  • RF is always preceded by pharyngitis:+ ASO test
  • acute glomerulonephritis is sometimes preceded by pharyngitis, giving a + ASO test, and some preceded by skin infections, giving a - ASO test

streptokinase or DNAse B antibodies develop in what diseases?

• streptococcal pharyngeal
• skin infections

what are the nonsuppurative sequelae of GAS infections?

• rheumatic fever and rheumatic heart disease
  • inflammatory changes involving the heart (endocarditis, pericarditis, myocarditis), joints (arthralgias to arthritis), blood vessels, and subcutaneous tissues
• acute glomerulonephritis
  • acute inflammation of the renal glomeruli with edema, hypertension, hematuria, and proteinuria

the most sensitive tool for testing pyogenic infections

not useful for nonsuppurative sequelae

the antigen detection for nonsuppurative diseases caused by S.pyogenes is low on sensitivity and high on specificity

sensivity: true positives/ (true positives + false negatives)

specificity: true negatives/ (true negatives + false positives)

so, there is a LOW false positive rate, but HIGH false negative rate. if you test a + ASO you are solid, but if you test a -ASO, need to f/u with culture

how would the three main Ab assay read in a typical rheumatic fever test?

since RF is always preceded by pharyngitis, its ASO would be + when Strep is present

anti-DNAse B would be +

anti-streptokinase would be +

how would the three main Ab assays read in the context of a test in acute glomerulonephritis?

ASO would be - (if preceded by skin infection) OR + (if preceded by pharyngitis)

*if you get a (-) ASO need to perform culture*

anti-DNAse B would be +

anti-streptokinase would be +

• penicillin, erythromycin, vancomycin
• antibiotic resistance is not a significant problem

what is useful in patients with recurrent rheumatic heart disease?

prophylaxis (penicillin) to prevent recurrent disease

even though risk of recurrent disease decreases over time, the risk of heart damage (valves injured --> endocarditis), especially before procedures are performed that can induce transient bacteremias (ie: dental procedures)

does recurrent disease occur in acute glomerulonephritis? what does this mean for prophylaxis?

recurrent disease does NOT occur with acute glomerulonephritis

prophylaxis is not indicated

Strep. agalactiae

• only group B member of clinical interest
• colonizes gut and genital tracts

what patient group is at increased risk of contraction of GBS?

• up to 20% healthy women's genital tracts are colonized
• may be acquired by fetus during vaginal delivery
• premature infants are at an increased risk of developing invasive disease with GBS w.o protective maternal Abs and low C' levels
  • early onset-acquired in utero or at birth (can cause sepsis, meningitis, pneumonia)
  • late onset-acquired exogenously (can cause sepsis, meningitis)

what are the best ways to detect GBS colonization in women or infants?

• antigen tests (DNAse, streptokinase, ASO should NOT BE USED)

• nucleic acid amplification tests are available and are sensitive as culture
• culture is *the gold standard* for detecting colonization or disease

• similar to GAS: penicillin is combined with aminoglycoside for serious infections
• vancomycin used for penicillin allergic pts
• prevention
  • culture or nucleic acid based tests for GBS are done on pregnant women near time of delivery
    • if +: penicillin given during delivery to prevent transmission and infection of newborn
    • cafazolin or vancomycin is used for penicillin-allergic women

what other beta-hemolytic strep groups cause infection?

• groups: 
  • S. dysgalactiae  Group C, G 
  • S. anginosus grp*  Group A, C, F, G, nongroupable
• can cause pharyngitis, abscess formation
• like other beta-hemolytic streptococci, they are highly susceptible to penicillin and related antibiotics