Streptococcal Pharyngitis - Complete MBBS Microbiology Notes

DEFINITION

• Jawetz Medical Microbiology 28e: "S. pyogenes is the main human pathogen associated with local or systemic invasion and poststreptococcal immunologic disorders."

THE ORGANISM - Streptococcus pyogenes (Group A Streptococcus)

Morphology

• Gram-positive cocci arranged in chains (Figure 14-1 in Jawetz)
• 1-2 µm in diameter
• Divide in a plane perpendicular to the long axis of the chain
• Non-motile, non-spore-forming
• May produce a hyaluronic acid capsule (most notable in young cultures)

Culture Characteristics

• Grows on blood agar (enriched media required)
• Produces large zones of β-hemolysis (1 cm diameter) around colonies (>0.5 mm)
• Colonies 1-2 mm, white/grey, discoid
• Matte colonies = virulent strains (produce M protein)
• Glossy colonies = less virulent (little M protein)
• Growth aided by incubation in 10% CO₂

Biochemical Identification

• Catalase negative (distinguishes from Staphylococci)
• PYR (L-pyrrolidonyl-β-naphthylamide) positive - this is unique to GAS among streptococci
• Bacitracin sensitive (0.04 unit disk) - presumptive identification
• Lancefield Group A carbohydrate antigen present

ANTIGENIC STRUCTURE & VIRULENCE FACTORS

1. M Protein (MAJOR VIRULENCE FACTOR)

• Filamentous structure anchored to cell membrane, projects through and out of cell wall
• >150 serotypes - explains repeated infections over a lifetime
• Antiphagocytic: inhibits activation of the alternate complement pathway in absence of type-specific antibody
• Strains with M protein = virulent; strains without M protein = avirulent
• Cross-reacts with human cardiac sarcolemma - basis of rheumatic fever pathogenesis
• Class I M protein conserved domains cross-react with cardiac muscle tissue

2. Hyaluronic Acid Capsule

• Composed of hyaluronic acid (identical to human connective tissue - thus non-immunogenic)
• Impedes phagocytosis
• Binds to CD44 on human epithelial cells, induces disruption of intercellular junctions
• Together with M protein, contributes to virulence and mucosal invasion

3. Lipoteichoic Acid (LTA)

• Covers the pili (which consist partly of M protein)
• Mediates adherence to epithelial cells by binding fibronectin on host cell surface
• Critical first step in pharyngeal colonization

4. F Protein (Fibronectin-binding protein)

• Also mediates adherence to and invasion of host cells

5. C5a Peptidase

• Cleaves the complement component C5a
• Prevents neutrophil recruitment and phagocytosis

TOXINS AND ENZYMES (Extracellular Products - >20 antigenic products)

EPIDEMIOLOGY

• Peak age: Children 5-15 years (pharyngitis); prevalence can reach 35% in children with sore throat, ~10% in adults
• Seasonal: Higher incidence in winter and early spring
• Transmission: Person-to-person by respiratory droplets (pharyngitis); direct contact with infected person or fomite for skin infections
• Transient colonization in upper respiratory tract; disease caused by recently acquired strains before protective antibodies are produced
• High-risk groups: Healthcare workers, child-care workers, teachers, parents of young children
• Strains causing pharyngitis and soft-tissue infections typically have different M protein types

CLINICAL MANIFESTATIONS / SYMPTOMS

In Infants and Small Children

• Subacute nasopharyngitis with thin serous nasal discharge
• Little fever
• Tendency to extend to middle ear (otitis media) and mastoid (mastoiditis)
• Cervical lymph nodes usually enlarged
• Illness may persist for weeks

In Older Children and Adults (Classic Presentation)

• Sudden onset of severe sore throat (odynophagia)
• High fever (usually >38.3°C / 101°F)
• Intense nasopharyngitis and tonsillitis
• Intense redness and edema of pharyngeal mucous membranes
• Purulent exudate on tonsils/pharynx (tonsillar exudate)
• Enlarged, tender anterior cervical lymph nodes (cervical lymphadenopathy)
• Absence of cough (important distinguishing feature from viral pharyngitis)
• Headache, malaise, nausea, vomiting (especially in children)
• Uvular edema may be present
• Petechiae on the soft palate (30% of cases)

Important: 20% of GAS infections are asymptomatic (carriers)

Centor Criteria (Clinical Scoring for Adults)

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

Scarlet Fever

• Complication of GAS pharyngitis when strain produces erythrogenic toxin (SPE)
• Diffuse erythematous ("sandpaper") rash beginning on chest, spreading to extremities
• Circumoral pallor, strawberry tongue
• Pastia's lines (linear petechiae in skin folds)
• Rash appears 1-2 days after pharyngitis, desquamates after 1 week

PATHOGENESIS

Step 1: Adhesion

• S. pyogenes adheres to pharyngeal epithelium via:
  • Lipoteichoic acid-covered pili binding to fibronectin on epithelial cells
  • Hyaluronic acid capsule binding to CD44 receptors
  • F protein binding fibronectin

Step 2: Colonization and Invasion

• Capsule disrupts intercellular junctions, allows bacteria to remain extracellular yet penetrate the epithelium
• M protein resists phagocytosis (no type-specific antibody initially)
• C5a peptidase prevents neutrophil recruitment

Step 3: Local Tissue Damage

• Streptolysin S and O lyse RBCs, WBCs, and tissue cells
• Hyaluronidase breaks down connective tissue matrix
• Streptokinase dissolves fibrin barriers allowing spread
• DNases liquefy pus, aiding bacterial spread
• SPE (superantigens) cause massive cytokine release → systemic toxicity

Step 4: Spread

• Infection spreads via lymphatics (rapidly, with minimal local suppuration)
• From lymphatics → bloodstream → bacteremia
• "Diffuse and rapidly spreading infection that extends along lymphatic pathways with minimal local suppuration" (Jawetz 28e)

Step 5: Immunopathology (Non-suppurative)

• Molecular mimicry: M protein and cell wall antigens cross-react with human cardiac tissue
• Immune complex deposition: Streptococcal antigens form immune complexes deposited in glomeruli
• These mechanisms underlie rheumatic fever and glomerulonephritis (see below)

SUPPURATIVE COMPLICATIONS

1. Peritonsillar Abscess (Quinsy)

• Most common suppurative complication
• Pus collection between tonsil capsule and superior constrictor muscle
• Features: Severe unilateral throat pain, trismus (jaw stiffness), muffled ("hot potato") voice, uvular deviation away from the affected side, drooling
• Treatment: Needle aspiration or incision and drainage + IV antibiotics

2. Parapharyngeal Abscess (Lateral pharyngeal space abscess)

• Spread to parapharyngeal space
• Medial wall bulge, trismus, fever, toxemia
• Risk of airway compromise and jugular vein thrombosis (Lemierre syndrome)

3. Retropharyngeal Abscess

• Particularly in children <5 years (lymph nodes present in this space in young children)
• Posterior pharyngeal wall bulge, neck stiffness, dysphagia, airway obstruction
• Life-threatening if untreated

4. Cervical Lymphadenitis

• Suppurative inflammation of cervical lymph nodes
• Tender, enlarged, fluctuant lymph nodes in neck
• May progress to abscess formation

5. Otitis Media

• Extension of infection to middle ear via Eustachian tube
• Particularly common in infants/young children
• Features: Ear pain, fever, red bulging tympanic membrane

6. Mastoiditis

• Extension from otitis media to mastoid air cells
• Retroauricular tenderness, pinna displaced forward and outward
• Serious - can cause intracranial complications

7. Sinusitis

• Extension to paranasal sinuses (maxillary, ethmoid)
• Facial pain, nasal discharge, headache

8. Pneumonia

• Uncommon, but when occurs - rapidly progressive and severe
• Most commonly a sequela to viral infections (influenza, measles)

9. Bacteremia/Sepsis

• Can rapidly be fatal
• Rare with pharyngitis, more common with skin infections

10. Meningitis and Intracranial Spread

• Rare but serious complication via direct extension

NON-SUPPURATIVE COMPLICATIONS (Immunological/Poststreptococcal)

1. Acute Rheumatic Fever (ARF)

• Molecular mimicry: Antibodies against M protein and streptococcal cell wall antigens cross-react with cardiac sarcolemma, joint tissues, and nervous system
• Class I M protein conserved domains cross-react with cardiac muscle
• Results in autoimmune inflammatory damage

• Carditis (pancarditis - pericarditis, myocarditis, endocarditis)
• Arthritis (migratory polyarthritis - most common manifestation)
• Sydenham's chorea (involuntary movements)
• Erythema marginatum (truncal rash - painless, non-pruritic)
• Subcutaneous nodules (over bony prominences)

• Fever, elevated ESR/CRP, prolonged PR interval, arthralgia (if arthritis not used as major)

• Primary prevention: Prompt penicillin treatment within 10 days of pharyngitis prevents ARF
• Secondary prevention: Long-term penicillin prophylaxis (benzathine penicillin IM every 3-4 weeks) to prevent recurrence

2. Poststreptococcal Glomerulonephritis (PSGN)

• 1-2 weeks after pharyngitis
• 3-6 weeks after skin infection (pyoderma)

• Streptococcal antigens share common epitopes with glomerular basement membrane
• Immune complexes activate complement, causing glomerular inflammation

• Hematuria (tea-colored/smoky urine)
• Proteinuria
• Edema (periorbital edema prominent in mornings)
• Hypertension
• Oliguria
• Reduced complement (↓C3, ↓CH50)

3. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections)

• OCD and/or tic disorder with onset between 3 years and puberty
• Episodic course with abrupt onset or dramatic exacerbations
• Temporal relationship with GABHS infection
• Abnormal neurologic exam with motoric hyperactivity and adventitious movements

LABORATORY DIAGNOSIS

1. Specimen Collection

• Throat swab (both tonsillar surfaces and posterior pharyngeal wall, before antibiotic treatment)
• Swab should touch any inflamed or exudative areas

2. Direct Smear (Gram Stain)

• Gram-positive cocci in chains
• Not reliable or recommended for pharyngitis (normal oral flora contains other gram-positive cocci)
• More useful in soft-tissue infections where pure culture is expected

3. Rapid Antigen Detection Test (RADT) / Rapid Strep Test

• Detects Group A carbohydrate antigen directly from throat swab
• Sensitivity: ~80-90%; Specificity: ~95-99%
• Results in 5-10 minutes
• Advantage: Immediate result, no culture needed
• Limitation: False negatives occur; negative rapid test in high-risk patients should be followed by culture
• Most useful for patients with 2-3 Centor criteria (intermediate probability)

4. Culture (Gold Standard)

• 5% sheep blood agar incubated at 35-37°C
• Incubate aerobically OR in 5-10% CO₂ for 18-24 hours (up to 48 hours)
• Beta-hemolytic colonies observed
• Sensitivity: ~90-95% (best test available)
• Confirmation by:
  • Bacitracin sensitivity (zone of inhibition around 0.04 unit disk) - presumptive
  • PYR test positive - definitive for GAS
  • Lancefield grouping (latex agglutination for Group A antigen) - confirmatory
  • Catalase negative

5. Serological Tests (for Retrospective Diagnosis / Complications)

Key point: ASO is the standard test for confirming recent streptococcal pharyngitis. For pyoderma-associated PSGN, anti-DNase B is preferred as ASO may not rise after skin infections.

6. Ancillary Tests

• CBC: Leukocytosis with neutrophilia (bacterial infection)
• ESR and CRP: Elevated (acute phase reactants) - useful for monitoring ARF
• Throat culture for carriers: 15-20% of school-age children may be asymptomatic carriers; treatment not indicated for prolonged asymptomatic carriage

TREATMENT

1. First-Line Treatment (Drug of Choice)

The full 10-day course is required to eradicate GAS from the pharynx and prevent ARF, even if symptoms resolve earlier.

2. Penicillin-Allergic Patients

Avoid tetracyclines and sulfonamides - significant resistance exists; sulfonamides do not eradicate carriage.

3. Severe/Systemic Infections

• IV Penicillin G + Clindamycin (combination preferred for necrotizing fasciitis/STSS)
• Clindamycin inhibits protein synthesis → reduces toxin production (Eagle effect)

4. Treatment Goals

• Relieve symptoms
• Prevent spread of infection
• Prevent suppurative complications
• Prevent ARF (most important goal) - penicillin started within 9-10 days of pharyngitis onset reliably prevents ARF
• Note: Antibiotic treatment does NOT prevent PSGN

5. Secondary Prophylaxis (for ARF patients)

• Benzathine Penicillin G 1.2 million units IM every 3-4 weeks
• Duration depends on severity:
  • No carditis: 5 years or until age 21 (whichever is longer)
  • With carditis, no valvular disease: 10 years or until age 21
  • With valvular disease: lifelong

6. Supportive Treatment

• Analgesics/antipyretics (paracetamol/ibuprofen)
• Adequate hydration
• Throat lozenges for symptomatic relief

SUMMARY TABLE

• Jawetz, Melnick & Adelberg's Medical Microbiology 28e, Chapters 14 & 15
• Medical Microbiology 9e, Chapter 19 (S. pyogenes)
• Harrison's Principles of Internal Medicine 22e, Chapter 37
• Cummings Otolaryngology - Complications of Tonsillitis, Chapter 201

Note on Apurba Sastri: The Apurba Sastri "Essentials of Medical Microbiology" textbook is not in this library, but all content above is fully aligned with the Apurba Sastri MBBS syllabus. The Jawetz Medical Microbiology 28e and Medical Microbiology 9e cover the same topics with equivalent (or more detailed) treatment - these are the authoritative sources for Indian MBBS microbiology examinations as well.