Upper Respiratory Tract Infections

Streptococci

• Classification based on C carbohydrate antigen on surface

• Medically important Lancefield Groups A, B, C, D

Hemolytic Activity Classification

• Alpha-hemolytic

  • Green, partial hemolysis

  • Pneumoniae & Viridans (mutans, sanguis)

• Beta-hemolytic

  • Clear, complete hemolysis

  • Pyogenes (Group A), agalactiae (Group B)

• Gamma-hemolytic

  • No hemolysis

  • Enterococcus (E. faecalis, E. faecium)

Group A Streptococci (GAS)

• Streptococcus pyogenes

  • Differentiated by M-protein (>124 serotypes)

  • Found on skin and mucus membranes of nasopharynx (often present asymptomatically)

• Key virulence factors

  • Role in pathogenesis

    • Adhesion

    • Interfere with immune system

GAS — Pore-Forming Toxins (Streptolysin O & S)

• Monomers of toxin protein are secreted by bacterium

• Monomers polymerize on target cell surface and insert themselves into membrane, releasing cell contents

• Key virulence factors

  • Exotoxins: SpeA-SpeG (not found in all Strep)

    • Encoded by phage

    • Disease specific - SpeA & SpeC are most severe

    • Super-antigen activity - overstimulate the immune system causing harm

    • Erythrogenic / pyrogenic

Streptococcal pharyngitis & Tonsillitis

• Scarlet fever

  • Severe form of pharyngitis

  • Results from Spe toxins entering the blood stream and stimulating inflammation response

• Rheumatic fever

  • Inflammatory damage to heart muscle in acute rheumatic fever results from cross reactivity between Streptococcal antigens & muscle antigens found on heart valve tissue (not infection)

    • Long term consequences: arterial fibrillation / cardiac failure

Corynebacterium diphteriae

• A-B type (binary) toxins

  • Toxin consists of two peptide chains

  • The B chain binds to receptors on the host cell and facilitates internilizations

  • The A chain enters the cell ad is the active component resulting in toxin activity

• Diphteria toxin (phage encoded) mode of action

  • ADP ribosylation of EF2 stops translation

    • Diphtheria toxin’s receptor-binding domain (B) binds host membrane

    • Membrane-bound toxin (A+B) enters by endocytosis

    • Catalytic subunit A is cleaved but held to the B subunit by disulfide bonds. Endosome vesicle acidifies; the disulfide bonds are reduced

    • The transmembrane domain facilitates passage of the catalytic A peptide through the vesicle membrane

    • The catalytic A domain ADP-ribosylates elongation factor 2 (EF2). This halts protein synthesis and kills the cell

• Pseudomembrane

  • Caused by diphtheria, covers the tonsils

  • Composed of necrotic fibrin, leukocytes, erythrocytes, epithelial cells, & organisms)

  • Adheres tightly to underlying tissue and bleeds with scraping

Bordetella pertussis - Virulence Factors

• Attachment and damage

  • FHA and PT are secreted by B pertussis and permit attachment to tracheal cells

  • Trachael cytotoxin can damage cilia and cells of trachea

  • Loss of cilia prevents removal of mucus which will build up in airway - coughing is attempting to remove this

  • Loss of basic defense leave individual prone to secondary infections

• Control and prevention

  • Antibiotics work best in prodromal stage. Much of the disease related to damage; regeneration needed

    • Prevents secondary infections

  • Acellular vaccine-purified PT and FHA, Pn & Fim

  • Vaccination

Pertussis Toxin

• Binary (A-B) toxin

  • ADP ribosylates proteins regulating adenylate cyclase

  • Interferes with cAMP levels and cellular signaling in a variety of tissues

  • Interferes with strong immune response and responsible for many of symptoms

Stages of Pertussis

• Duration

  • Incubation: 7-10 days

  • Catarrhal: 1-2 weeks

  • Paroxysmal: 2-4 weeks

  • Convalescent: 3-4 weeks (or longer)

• Symptoms

  • Incubation: none

  • Catarrhal: rhinorrhea, malaise, fever, sneezing, anorexia

  • Paroxysmal: repetitive cough with whoops, vomiting, leukocytosis

  • Convalescent: diminished paroxysmol cough, development of secondary complications (pneumonia, seizures, encephalopathy)

Meningitis

• Begins in the upper respiratory tract

• Signs, symptoms, and sequelae of acute bacterial meningitis are due to the inflammatory response to bacteria and bacterial products in the brain

  • Severe headache, stiff neck, photophobia, fever/vomiting, drowsy & less responsive / vacant, rash (neisseria)

• Cerebrospinal fluid (CSF) cloudiness / turbidity

  • CSF is supposed to be crystal clear

  • If not, there is likely meningitis

Bacterium & Meningitis

• Colonize nasopharynx

• Can colonize asymptomatically

• Not uncommon to be colonized

• Transmitted by respiratory droplet

  • Neisseria meningitidis - most common

  • Streptococcus pneumoniae - common in adults / older children

  • Haemophilus influenzae - common for 0-5 yr olds

Meningococcemia - Neisseria Meningitidis Infection

• Asymptomatic colonization of 2-5% but approaches 90% in “closed populations”

  • Purpura or petechial lesions give a rash like appearance

Meningitis - Virulence Factors

• Polysaccharide capsules

  • Vaccines to capsule antigens provide opsonizing Ab

  • Block phagocytosis by immune cells

• IgA protease

  • Antibody in mucus

• Lipooligo-saccharides, lipoteichoic acids, and peptidoglycan trigger inflammatory response

Bacterial Avoidance of Phagocytosis

• Capsules can cover the bacterial molecules recognized by phagocytes

• Less virulent strains of these same bacteria are often associated with milder upper respiratory infection

  • These may be secondary infections following cold / flu