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Str Pyo+ Sequelae

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  • 1. Streptococcus pyogenes Dr Kamran Afzal FCPS Microbiology
  • 2.
    • Case history
    • A 10-year-old female patient presents with a 2-day history of fever and sore joints. Further questioning reveals that she had a sore throat 3 weeks ago but did not seek any medical help at that time. Her current illness began with fever and a sore and swollen right knee. The following day her knee improved but her left elbow became sore and swollen.
  • 3. The Genus Streptococcus
    • FAMILY Streptococcaceae
    • Some important pathogens, commensals of mucous membranes
    • Opportunistic pathogens
    • 40 species, in 6 clusters
    • Strong fermenters of carbohydrates -> Lactic acid
    • Facultative anaerobes
    • Peptostreptococci are obligate anaerobes
  • 4. Clinically Important Streptococcus species γ No S. mutans Mutans α D S. bovis Bovis γ K S. salivarius Salivarius α G, F S. anginosus Anginosus α α α O O H S. pneumoniae S. mitis S. sanguis Mitis β β β A B C S. pyogenes S. agalactiae S. eqisimilus Pyogenic Type of Haemolysis Lancefield Group Species Group
  • 5. Typing of Streptococci
    • Haemolytic activity
      • Haemolysis on sheep blood agar
      • α, β or γ
    • Lancefield grouping
      • Polysaccharide antigen in cell wall
      • 21 serological groups (A-H and K-W)
    • M protein
      • 80 serotypes
    • Molecular biology
      • PCR, RFLP, DNA sequencing
  • 6. Haemolytic Activity
    • β Haemolysis
      • Complete lysis/clearing of RBCs induced by bacterial haemolysins
    • α Haemolysis
      • Incomplete haemolysis of RBCs
      • H 2 O 2 oxidizes Hb -> Methaemoglobin (greenish)
    • γ Haemolysis
      • No
      • haemolysis
  • 7. Characteristics - S. pyogenes
    • Gram positive
    • Arranged in chains
    • β hemolytic on blood agar
    • Bacitracin sensitive
    • Catalase negative
    • Lancefield Serological Group A
    • Non-motile
    • Non-sporing
    • PYR positive
  • 8. Pathogenesis
    • Virulence factors
      • Evasion of host immunity
      • Adherence
      • Tissue damage
  • 9. Virulence Factors
    • F protein
      • Adhesion with fibronectin
    • M protein
      • Resist phagocytosis
    • Capsule
      • Hyaluronic acid, producing mucoid colonies
      • Anti-phagocytic effect
    • Streptolysins
      • Streptolysin O (O 2 labile)
        • ASOT of antibodies detected in serum after severe infection
      • Streptolysin S (Serum-soluble)
        • β haemolysis
  • 10.
    • C5a peptidase
      • Cleaves human C5a, which is a potent chemo-attractant
    • Pyrogenic exotoxins
      • SPE A, SPE B and SPE C
      • Release of IL-1, IL-2, INF- γ and TNF
    • Hyaluronidase
      • Degrade hyaluronic acid, spread in fascial planes
    • Streptokinase
      • Degrades building up of fibrin barriers, rapid spread
    • Lipoproteinase
      • Opacity factor: induces opalescence in serum
    • DNAse
      • Hydrolyses nucleic acids, spread by liquifying viscious exudates
  • 11.  
  • 12. Clinical Features
  • 13. Transmission
    • Spread
      • Person to person
        • Respiratory droplets
      • Direct contact
        • Infected wounds/sores
    • Asymptomatic pharyngeal carriage
      • All age groups, most common among children
  • 14. Diseases caused by S. pyogenes
  • 15. Diseases caused by S. pyogenes
    • Invasive disease
      • Cellulitis
      • Necrotizing fasciitis [NF]
      • Myositis
      • Toxic shock-like syndrome [STSS]
      • Bacteraemia
      • Pneumonia
      • Puerperal sepsis
    • Non-invasive disease
      • Strep throat
      • Impetigo
      • Erysipelas
    • Non-suppurative sequelae
      • Acute rheumatic fever
      • Post-streptococcal glomerulonephritis
  • 16. Risk Groups
    • Invasive disease
      • Elderly, immuno-suppressed, persons with chronic cardiac or respiratory disease, diabetes, skin lesions (i.e. children with varicella [chicken pox], persons with penetrating trauma or surgical wounds, intravenous drug users)
    • Non-invasive disease
      • Children (5-10 yrs) at highest risk
  • 17. Strep Throat
    • Most common of all Strep diseases
    • Spread by saliva or nasal secretions
    • Abrupt onset of sore throat, fever, malaise
    • Posterior pharynx is reddened with enlarged tonsils and pus/exudate in crypts
    • Important to treat immediately to avoid post strep diseases
    • 20% school children carriers
  • 18. Impetigo
      • Lesions on extremities
      • Common on face
      • Pustular and crusty
  • 19. Erysipelas
    • Acute infection and inflammation of the dermal layer of skin
    • Painful red patches which enlarge and thicken
      • Infection involves the dermis and lymphatics
      • Characterized by intense erythema, induration and a sharply demarcated border
  • 20. Scarlet Fever
    • Diffuse erythematous rash over skin and mucous membranes
    • Rash develops within 1-2 days following pharyngitis , initially on upper chest, then spreads to extremities
    • The tongue becomes red and denuded – Strawberry tongue
    • Erythrogenic toxins: rash of scarlet fever
  • 21.
    • “ Flesh-eating bacteria”
    • Progresses very rapidly destroying fat and fascia
    • Rapid development of shock, MODS
    Necrotizing Fasciitis
  • 22. Streptococcal Myositis
    • Post-pharyngitis
    • Bacteraemic spread to the muscle
    • Infection may be precipitated by trauma or muscle sprain
  • 23. Streptococcal Toxic Shock Syndrome
    • Due to the release of streptococcal toxins into the bloodstream
    • Severe pain at the site of infection, soft tissue
    • Fever, malaise, vomiting, diarrhea, dizziness, confusion
    • A flat rash over large parts of the body
    • May progresses to shock and MODS
    • Multi-organ failure (2 or more of the following)
        • Hepatic involvement
        • Renal involvement
        • ARDS
        • Hematologic involvement
  • 24. Treatment
    • Penicillin G parenterally (Sensitive)
    • Other beta-lactam antibiotics
    • Erythromycin or other macrolides
    • Surgical resection/debridement
    • Supportive care
  • 25. Post-Streptococcal diseases (Sequelae)
  • 26. Post-streptococcal Diseases Immune Mediated
    • Acute rheumatic fever (ARF)
    • Post-streptococcal glomerulonephritis (AGN)
    • Post- streptococcal reactive arthritis
    • Sydenhams chorea
    • Erythema nodosum
    • Cutaneous polyarteritis nodosa (PAN)
    • Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS)
  • 27. Rheumatic Fever
    • Most common cause of permanent heart valve damage in children
    • Antibody cross reactivity between the cell wall of S. pyogenes and heart muscle or joint tissue
    • Diagnosis is based on symptoms and is difficult
    • Ages 6 - 15
  • 28. Pathogenesis
    • Follows GAS pharyngitis
    • Antibody against M-protein cross react with host tissue
    • 2-3 weeks after pharyngitis – immune mediated
    • Fibrinoid degeneration, inflammation mediated by T lymphocytes and macrophages
    • Heart, skin, brain and joints
  • 29. Pathology
    • Acute Rheumatic Fever
      • Acute inflammatory phase
      • Heart – Pancarditis
      • Skin – Erythema marginatum
      • CNS – Sydenham’s chorea
      • Migratory polyarthritis
    • Chronic Rheumatic Fever
      • Deforming fibrotic valvular disease
        • Fish Mouth Mitral Stenosis
  • 30. Acute Rheumatic Carditis
    • Aschoff bodies
      • Aschoff giant cells
      • Anitschkow cells
      • Fibrinoid degeneration
      • T lymphocytes
  • 31. Jones Criteria of Diagnosis
    • Major Criteria
    • Migratory polyarthritis
    • Carditis
    • Subcutaneous nodules
    • Erythema marginatum
    • Sydenham’s chorea
    • Minor Criteria
    • Nonspecific symptoms
    • Fever
    • Arthralgia
    • Acute phase reactants
    • High ESR
    For Diagnosis: Two Major or One Major and Two Minor Criteria following GAS pharyngitis
  • 32. Laboratory Investigations
    • No specific laboratory investigations
    • Cultures are usually negative
    • High ASO titre
    • High Anti-DNAse B titres
    • High Acute phase reactants –
      • CRP, SAP, Complements, Coagulation Proteins
  • 33.
    • Anti-streptococcal therapy
      • Benzathine penicillin (long acting) 1.2 million units once (IM injection) or oral penicillin 10 days, if allergic to penicillin erythromycin for 10 days
    • Antibiotic is given even if throat culture is negative
    • Salicylates (Aspirin derivatives)
    • Corticosteroids to decrease inflammation and fever
    Treatment
  • 34. Post-Streptococcal Glomerulonephritis
    • Pathogenesis
    • Follows GAS infection of skin (or pharynx)
    • Antibody against M protein cross reacts between the cell wall of S. pyogenes and glomeruli of the kidney
    • Deposition of Ag-Ab complexes, activation of complement (C3)
    • Characterized by damage to glomeruli of kidneys due to inflammatory response
  • 35. Pathology Post-streptococcal glomerulonephritis is immunologically mediated, and the immune deposits are distributed in the capillary loops in a granular, bumpy pattern because of the focal nature of the deposition process
  • 36. Clinical Features
    • Most common in children 2-12 yrs
    • Symptoms occur 10-21 days after infection
      • Haematuria
      • Proteinuria
      • Decreased GFR, oliguria
      • Hypertension
      • Edema around eyes, feet and ankles
      • Ascites or pleural effusion
  • 37. Laboratory Investigations
    • No specific laboratory investigations
    • Cultures are usually negative
    • Low C3
    • Normal C4
    • Normal/High Antistreptolysin O titre (ASOT)
    • Kidney biopsy
      • Immune complex mediated inflammation and proliferation of glomeruli
  • 38. Treatment and Recovery
    • Conservative management
    • Penicillin or Erythromycin to eradicate the residual strep infection
    • 99% complete recovery in children and 85% in adults
    • Kidney damage in the remainder is often permanent resulting in chronic glomerular nephritis
  • 39. Diseases caused by S. pyogenes
    • Invasive disease
      • Cellulitis
      • Necrotizing fasciitis [NF]
      • Myositis
      • Toxic shock-like syndrome [STSS]
      • Bacteraemia
      • Pneumonia
      • Puerperal sepsis
    • Non-invasive disease
      • Strep throat
      • Impetigo
      • Erysipelas
    • Non-suppurative sequelae
      • Acute rheumatic fever
      • Post-streptococcal glomerulonephritis
  • 40.
    • Case history
    • A 10-year-old female patient presents with a 2-day history of fever and sore joints. Further questioning reveals that she had a sore throat 3 weeks ago but did not seek any medical help at that time. Her current illness began with fever and a sore and swollen right knee. The following day her knee improved but her left elbow became sore and swollen.
    • Acute Rheumatic Fever
  • 41.