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Streptococcal Pharyngitis - Comprehensive Notes (2nd Year MBBS Microbiology)

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1. Definition

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2. Organism: Streptococcus pyogenes (GAS)

• Hyaluronic acid capsule
• M protein and lipoteichoic acid (LTA) projecting via pili
• Lancefield group A carbohydrate antigen
• Peptidoglycan matrix

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3. Epidemiology

• Age: Most common in children 5-15 years old (peak school age); adults affected less frequently (~10% of sore throats vs. up to 35% in children)
• Season: Higher prevalence in winter and early spring
• Transmission: Person-to-person via respiratory droplets from infected individuals or carriers; nasal discharge is the most dangerous source
• Carriage: Humans can be asymptomatic nasopharyngeal carriers; disease occurs when recently acquired strains colonize before protective antibodies develop
• Risk groups: Healthcare workers, child-care workers, teachers, parents of young children, military/institutional settings
• Pharyngitis and soft-tissue infections are caused by strains with different M protein types

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4. Virulence Factors and Pathogenesis

4.1 Virulence Factors

• Fibrillar coiled-coil molecule with structural homology to myosin
• Carboxy terminus rooted in peptidoglycan; amino terminus extends outward

• 100 serotypes - basis of typing

• Antiphagocytic: Binds serum Factor H, causing reduced deposition of C3b (complement component) on the bacterial surface - evades opsonophagocytosis
• Type-specific M protein antibodies confer protective immunity
• Molecular mimicry with cardiac myosin - important in Acute Rheumatic Fever (ARF)

• Impedes phagocytosis
• Binds to CD44 on human epithelial cells - disrupts intercellular junctions, facilitating tissue penetration
• Important in resurgence of rheumatic fever
• "Stealth" - camouflages organism as "self" (hyaluronic acid is also in host tissues)

• Mediate binding to fibronectin on host epithelial cell surfaces
• Initial attachment step

• Inactivates complement component C5a
• Blocks chemotaxis of polymorphonuclear neutrophils (PMNs) to infection site
• Second major antiphagocytic mechanism

• Protein (MW 60,000), oxygen-labile (active only in reduced state)
• Lyses erythrocytes, leukocytes, platelets
• Antigenic - stimulates anti-streptolysin O (ASO) antibody formation
• ASO titer >160-200 units = abnormally high; indicates recent GAS infection
• Responsible for deep hemolysis in blood agar cuts

• Oxygen-stable, surface-active hemolysin
• Causes hemolytic zones around surface colonies on blood agar
• Not antigenic
• Toxic to phagocytic cells

• Dissolves fibrin clots - aids in spreading infection
• Antigenic (anti-streptokinase antibodies form)

• Splits hyaluronic acid in connective tissue ground substance
• Facilitates spread through tissues
• Antigenic

• Depolymerizes DNA in pus
• Reduces viscosity of exudate - aids spread
• Anti-DNase B test used in glomerulonephritis diagnosis

• Three types: SpeA, SpeB, SpeC
• SpeA: encoded by a lysogenic phage; associated with Streptococcal Toxic Shock Syndrome (STSS) and scarlet fever
• Act as superantigens - bind MHC class II and V-beta region of TCR without normal antigen processing
• Massive non-specific T-cell activation - cytokine storm - shock and tissue injury
• SpeB: potent protease, interferes with phagocytosis

4.2 Pathogenesis of Pharyngitis

1. Attachment: LTA and Protein F bind fibronectin on pharyngeal epithelial cells; M protein pili make initial contact
2. Colonization: Hyaluronic acid capsule binds CD44 on epithelial cells; capsule disrupts intercellular junctions
3. Evasion of innate immunity:
   • M protein binds Factor H → impairs C3b deposition → resists phagocytosis
   • C5a peptidase → reduces PMN chemotaxis
4. Tissue injury: Streptolysins O and S cause direct cytotoxic damage; streptokinase, hyaluronidase, and DNases prevent localization of infection
5. Inflammatory response: Intense local inflammation, exudate formation on tonsils and posterior pharynx

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5. Clinical Manifestations and Symptoms

5.1 Typical Symptoms

• Sudden onset sore throat (most prominent symptom)
• Fever (usually >38.5°C)
• Odynophagia (painful swallowing)
• Headache
• Malaise and fatigue
• Nausea, vomiting, abdominal pain (especially in children)
• Absence of cough (important distinguishing feature from viral pharyngitis)
• Absence of rhinorrhea

5.2 Clinical Signs

• Tonsillar erythema with or without exudate (white/yellowish-grey patches)
• Petechiae on soft palate (characteristic but not pathognomonic)
• Tender anterior cervical lymphadenopathy (anterior cervical adenitis)
• Uvular edema and erythema
• Sandpaper-like skin rash (scarlet fever - when SPEs are produced)
• Strawberry tongue (in scarlet fever)

5.3 Centor Scoring System (Clinical Diagnosis Aid)

1. History of fever
2. Absence of cough
3. Tender anterior cervical lymphadenopathy
4. Tonsillar exudate or swelling

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6. Complications

6.1 Suppurative (Direct Spread) Complications

6.2 Non-Suppurative (Post-Streptococcal/Immunological) Complications

A. Acute Rheumatic Fever (ARF)

• Latent period: 2-4 weeks after GAS pharyngitis (NOT skin infection)
• Mechanism (autoimmune - molecular mimicry):
  • M protein shares structural epitopes with cardiac myosin, sarcolemmal proteins, and valve endothelium
  • Antibodies against streptococcal M protein cross-react with cardiac tissue
  • T-cells also cross-react - causing pancarditis
• Manifestations (Jones Criteria):
  • Carditis (most serious - mitral/aortic valvular damage)
  • Polyarthritis (migratory, most common)
  • Sydenham's chorea (St. Vitus' dance)
  • Subcutaneous nodules
  • Erythema marginatum
• Note: Only pharyngitis (not pyoderma/skin infection) causes ARF
• Prevention: Adequate penicillin treatment within 10 days prevents ARF

B. Post-Streptococcal Glomerulonephritis (PSGN)

• Latent period:
  • 1-4 weeks after pharyngitis
  • 3-6 weeks after skin infection (impetigo/pyoderma)
• Mechanism: Immune complex deposition in glomeruli (Type III hypersensitivity)
  • Circulating antigen-antibody complexes deposit in glomerular basement membrane
  • Complement activation → inflammatory damage
• Caused by: Only specific nephritogenic strains (e.g., M types 1, 4, 12 for pharyngitis; M type 49 for skin infection)
• Clinical features: Edema, hypertension, hematuria (cola-colored urine), proteinuria, decreased serum complement (C3)
• Pathology: Diffuse proliferative glomerulonephritis
• Prognosis: Usually benign; self-limiting over weeks-months. Occasionally progresses to renal failure.
• Important: Antibiotic treatment does NOT prevent PSGN (unlike ARF)

C. Other Post-streptococcal Sequelae (Less Common)

• PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) - OCD, tics
• Post-streptococcal reactive arthritis
• Erythema nodosum

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7. Laboratory Diagnosis

7.1 Specimen Collection

• Throat swab - posterior pharynx, tonsils, and tonsillar crypts (must avoid tongue and buccal mucosa)

7.2 Direct Microscopy (Gram Stain)

• Not useful for pharyngitis diagnosis
• Gram-positive cocci in chains
• Not helpful because other streptococci are part of normal pharyngeal flora
• Useful in soft tissue infections (sterile sites)

7.3 Culture (Gold Standard)

• Medium: 5% sheep blood agar (SBA)
• Incubation: 37°C for 24-48 hours; anaerobic incubation preferred (reveals β-hemolysis by both SLO and SLS; aerobic incubation may miss strains lacking SLS)
• Appearance: Small (0.5-1 mm), gray-white, transparent colonies surrounded by a clear zone of beta-hemolysis (2-3 mm)
• Plates with a stabbed/cut medium reveal deep hemolysis from SLO

7.4 Identification of GAS from Culture

7.5 Rapid Antigen Detection Test (RADT)

• Detects Group A carbohydrate antigen directly from throat swab
• Results in 5-10 minutes
• Specificity ~95-99% (very specific - positive result reliable)
• Sensitivity ~70-90% (less sensitive - negative result should be confirmed by culture)
• Based on enzyme immunoassay or latex agglutination
• Recommended for patients with Centor score 2-3

7.6 Molecular Methods

• PCR for GAS detection - high sensitivity and specificity
• Used in reference labs; identifies Lancefield group antigen genes

7.7 Serological Tests (for Non-suppurative Complications)

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8. Treatment

8.1 Goals of Treatment

1. Relieve symptoms
2. Prevent suppurative complications
3. Prevent non-suppurative complications (especially ARF)
4. Prevent transmission

8.2 Antibiotic Treatment

8.3 Antibiotic Resistance

• Penicillin: GAS has NEVER developed resistance - penicillin remains fully effective
• Erythromycin/Macrolides: Resistance is increasing; use with caution
• Tetracyclines: Resistance is common; NOT recommended

8.4 Symptomatic Treatment

• Analgesics/antipyretics: Paracetamol or NSAIDs for fever and pain
• Adequate hydration
• Note: Aspirin should be avoided in children (risk of Reye's syndrome)

8.5 Chemoprophylaxis

• Benzathine Penicillin G: 1.2 million units IM every 3-4 weeks (most reliable)
• OR Penicillin V 250 mg orally twice daily
• OR Sulfadiazine 1 g orally once daily
• Duration: Continued for years in children; at least 5 years after last attack or until age 21 (whichever is longer)
• Rationale: First attack of RF rarely causes severe cardiac damage; recurrences cause progressive valve damage

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Quick Summary Table

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Sources: Jawetz, Melnick & Adelberg's Medical Microbiology 28E | Sherris & Ryan's Medical Microbiology 8E | Medical Microbiology 9e (Murray et al.) | Harrison's Principles of Internal Medicine 22E