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STREPTOCOCCI Study Notes

Learning Outcomes

  • By the end of this unit, students should demonstrate competency in the following topics on Streptococci:
    • Provide theory and methodologies involved in understanding the mechanisms of virulence and pathogenicity of viral and bacterial pathogens.
    • Discuss the diagnostics principles for the isolation and identification of bacteria using molecular, culture-based, biochemical, and serological methods.
    • Explain various diseases caused by bacterial and their immunological impact.

Classification of Streptococci

  • Based on oxygen requirement:
    • Aerobes
    • Facultative Anaerobes
    • Obligate Anaerobes
  • Based on hemolysis on blood agar:
    • Alpha (α) Hemolytic: Viridans group. Classified into species by physiological and biochemical properties.
    • Beta (β) Hemolytic: Serological classification based on group-specific C carbohydrate antigen. Contains 20 Lancefield groups (A-G, K-L, M-N, O-T, U-V). Group A example - Streptococcus pyogenes.
    • Gamma (γ) Hemolytic: Enterococcus group; classified into species by physiological and biochemical properties.

Morphology of Streptococci

  • Physical Characteristics:
    • Cocci that are spherical or oval in shape, measuring approximately 0.5–1.0 μm in diameter.
    • Arranged in chains due to division in one plane; daughter cells typically do not separate.
    • Some strains possess a capsule primarily made of hyaluronic acid.

Cultural Characteristics

  • Streptococci require specific nutrients and are fastidious:
    • On blood agar: Colonies appear small, circular, with a clear zone of hemolysis.
    • In liquid media: Exhibit granular turbidity and a powdery deposit, typically observed in glucose or serum broth.

Biochemical Reactions

  • Key Characteristics:
    • Catalase negative (unlike staphylococci).
    • Not soluble in 10% bile (unlike pneumococci).
    • Positive for Pyrolidonyl-Beta-naphthylamide (PYR) test.
    • Failure to ferment ribose assists in distinguishing S. pyogenes from other streptococci.

Resistance

  • Susceptibility Factors:
    • Easily destroyed by heat (e.g., 54°C for 30 min).
    • Rapidly inactivated by antiseptics.
    • Resistant to crystal violet and other selective media such as crystal violet, nalidixic acid, and colistin sulphate.
    • Streptococcus does not develop antibiotic resistance.

Antigenic Structure

  • Components:
    • Capsule that inhibits phagocytosis.
    • Cell wall composed of three layers:
    • Outer layer: protein and lipoteichoic acid.
    • Middle layer: group-specific carbohydrate.
    • Inner layer: peptidoglycan.
    • Presence of hair-like pili that project through the capsule, composed of M protein and covered with lipoteichoic acid, promoting attachment to epithelial cells.

Toxins and Virulence Factors

  • Streptococcal Pyrogenic Exotoxins (SPE):
    • Three types (A, B, and C) act as superantigens, analogous to staphylococcal enterotoxins and TSS toxin.
    • They function as T cell mitogens that provoke a massive release of inflammatory cytokines, leading to symptoms such as fever, shock, and tissue damage.

Pathogenicity

  • Disease Classification:
    • Suppurative: Direct pus-producing infections.
    • Non-Suppurative: Includes sequelae from post-streptococcal infections.
    • Common Disease Causers by S. pyogenes: Pyogenic lesions that exhibit a tendency to spread.

Suppurative Streptococcal Diseases

  • Various infections include:
    1. Respiratory Infections:
    • Primary site of invasion is the throat, causing sore throat (tonsillitis and pharyngitis).
    • Can lead to suppurative complications such as otitis media, mastoiditis, quinsy, Ludwig’s angina, and suppurative adenitis.
    1. Skin and Soft Tissue Infections:
    • Characterized by conditions such as Erysipelas and Impetigo.
    • S. pyogenes commonly causes suppurative infections in wounds or burns, often resulting in cellulitis or lymphangitis.
Erysipelas
  • Description:
    • A diffuse infection that affects the superficial lymphatics.
    • Affected areas become red, swollen, and markedly demarcated from surrounding healthy skin, typically observed in older patients.
Impetigo
  • Characteristics:
    • Caused primarily by higher numbered serotypes of S. pyogenes.
    • Common presentations include throat infections and infections of scabies lesions, which can lead to acute glomerulonephritis in children from tropical regions.
Subcutaneous Infections
  • Range from cellulitis to necrotizing fasciitis, wherein mixed aerobic and anaerobic infections are common.
    • Necrotizing fasciitis may involve S. pyogenes M types 1 and 3, with associated pyrogenic exotoxin A contributing to severe soft tissue destruction often termed as ‘flesh-eating disease’.

Genital Infections

  • Details:
    • Composed of both aerobic and anaerobic streptococci, which are normally found in the female genital tract.
    • S. pyogenes is implicated in puerperal sepsis.
    • Historical significance: Ignaz Semmelweis emphasized handwashing in 1847 to prevent outbreaks of puerperal fever, a condition more recently recognized to stem from endogenous infections with anaerobic cocci.

Non-Suppurative Diseases

  • Sequels:
    • Two notable sequelae include acute rheumatic fever and acute glomerulonephritis.
    • Onset occurs between 1 to 3 weeks following an initial streptococcal infection, often without detectable organisms at the time of sequelae.
Acute Rheumatic Fever
  • Key Features:
    • The primary lesion involves carditis characterized by connective tissue degeneration of heart valves and inflammatory myocardial lesions marked by Aschoff nodules.
    • Typically follows persistent or repeated throat infections of streptococci alongside a robust antibody response.
Glomerulonephritis
  • Etiology:
    • Linked to a select few ‘nephritogenic’ strains of S. pyogenes, especially observable in tropical regions following skin infections.
    • Antigenic cross-reactions may occur between glomerular membrane antigen and cell membranes of nephritogenic streptococci, contributing to immune complex diseases.

Epidemiology

  • Source:
    • S. pyogenes resides primarily in the human upper respiratory tract, present in both patients and asymptomatic carriers.
  • Transmission Factors:
    • Spread occurs via direct contact, contaminated hands, dust, or fomites.
    • Higher incidence in children aged 5–8 years, predominantly in winter for temperate regions, while tropical regions show no seasonal variations.
    • Crowding is a critical factor leading to the transmission of infections, especially in closed communities.

Laboratory Diagnosis

  • Acute Infections:
    • Diagnosed confirmed via culture methods.
  • Non-Suppurative Complications:
    • Diagnosed through antibody demonstration.
Specimen Collection
  • Appropriate specimens include throat swabs, pus, or exudates.
  • Sera samples are utilized in cases of rheumatic fever or glomerulonephritis.
Microscopy and Culture
  • Microscopy:
    • Gram-stained films from pus can provide presumptive identification. Stained smears from the throat are usually non-diagnostic.
  • Culture Conditions:
    • Collect samples for immediate plating or transportation in Pike’s medium.
    • Specimens should be plated on sheep blood agar incubated at 37°C under 5–10% CO₂ or anaerobically.
Identification Techniques
  • Hemolytic streptococci grouped via the Lancefield technique employing specific antisera.
  • Rapid diagnostic methods include detection of group A streptococcal antigen and bacitracin sensitivity to confirm S. pyogenes.
Serology
  • For rheumatic fever and glomerulonephritis: Retrospective diagnosis relies on antistreptolysin O titration (ASO) where a titer over 200 indicates a previous streptococcal infection.

Prophylaxis

  • Rheumatic Fever:
    • Long-term penicillin administration is recommended for children showing early signs of rheumatic fever to avert reinfection and potential heart valve damage.
    • Not deemed effective for glomerulonephritis as it follows a singular streptococcal infection.

Treatment Approaches

  • All beta-hemolytic Group A streptococci are susceptible to penicillin G.
  • Alternatives for those allergic to penicillin include erythromycin or cephalexin.
  • Tetracyclines and sulphonamides are not recommended as treatment options.
  • Antimicrobials are ineffective against established glomerulonephritis and rheumatic fever.

Group B Streptococci

  • Notable pathogens affecting cattle often causing bovine mastitis.
  • Streptococcus agalactiae is a significant human pathogen responsible for:
    • Neonatal infections: including meningitis, arthritis, osteomyelitis, conjunctivitis, respiratory infections, peritonitis, omphalitis, and endocarditis.
    • Adult infections: resulting in conditions like puerperal sepsis and pneumonia.
Neonatal Infections
  • Most commonly classified as:
    • Early Onset Type: Occurs within a week of birth, presenting primarily as meningitis and septicemia.
    • Late Onset Type: Develops between the second and twelfth weeks of life, often presenting as septicemia.

Other Group B Infections in Neonates

  • Additional risks include arthritis, osteomyelitis, conjunctivitis, respiratory infections, peritonitis, omphalitis, and endocarditis.

Group B Infections in Adults

  • Common infections associated with Group B Streptococci include puerperal sepsis and pneumonia.
CAMP Test
  • Definition:
    • Demonstrated by accentuated zones of hemolysis showing when S. agalactiae is placed perpendicular to a streak of S. aureus on blood agar, named the Christie, Atkins, and Munch-Peterson (CAMP) test.

Group C Streptococci

  • Primarily animal pathogens belonging to species such as S. equisimilis.
  • Cause conditions such as:
    • Upper respiratory tract infections
    • Deep infections: endocarditis, osteomyelitis, brain abscesses, pneumonia, and puerperal sepsis.
    • Noteworthy source of streptokinase used in thrombolytic therapy for patients.

Enterococcus Species

  • Considered enterococci or fecal streptococci, distinguished from streptococci by:
    • Growth on MacConkey medium forming tiny pink colonies.
    • Resistance to heat (able to withstand 60°C for 30 minutes).
    • Characteristic morphology: pairs of oval cocci arranged at angles to each other; non-hemolytic.
Characteristics of Enterococci
  • Present in the intestines and gastrointestinal tract.
  • Frequently isolated from urinary tract infections (UTI) and wound infections.
  • Can cause serious conditions such as endocarditis, septicemia, and intra-abdominal abscesses.
Antimicrobial Resistance in Enterococci
  • Intrinsically resistant to cephalosporins and exhibit low-level resistance to aminoglycosides.
  • In strains showing high-level resistance to aminoglycosides, vancomycin is considered the drug of choice.
  • Vancomycin-resistant enterococci (VRE) have emerged, primarily due to alterations in the D-alanyl-D-alanine chain in the cell wall, contributing to resistance mechanisms.

Viridans Group

  • Composed of streptococci resident in the mouth and upper respiratory tract exhibiting alpha-hemolysis on blood agar.
  • Predominantly cause diseases in individuals with pre-existing cardiac lesions, leading to bacterial endocarditis.
  • May follow dental procedures or tooth extractions, causing transient bacteremia, and can implant on damaged prosthetic valves.
  • Prophylactic antibiotics are recommended prior to dental procedures to prevent infective endocarditis.