Case 4: Nabil Assad - Strep Pharyngitis

Virus

Small infectious particle relying on host cell to reproduce

• Cannot reproduce without host cell

Virus Structure

Capsid: Protein shell around nucleic acid

• Nucleocapsid: Capsid + nucleic acid

Envelope: Lipid membrane around capsid

• Matrix Proteins: Connect envelope to capsid

• No Envelope = Nonenveloped

Shape:

• Helical: Capsid proteins around nucleic acid in spiral rod

• Icosahedral: 20-sided shell surrounding capsid

• Complex: Abnormal shapes

Virus Classifications

Baltimore Classification System: By genome and replication strategy

• Class I: dsDNA

• Class II: ssDNA

• Class III: dsRNA

• Class IV: + sense ssRNA

• Class V: - sense ssRNA

• Class VI: Reverse transcription RNA

• Class VII: Reverse transcription DNA

Bacteria

Unicellular prokaryotes

Bacteria Structure

Cell Wall: Peptidoglycan

• Gram+ only

Outer Membrane: Endotoxins and phospholipids

• Gram- only

Cytoplasmic Membrane: Phospholipid bilayer

Capsule: Polysaccharide layers

Glycocalyx: Polysaccharide slime layers

Periplasm: Space between outer and cytoplasmic membranes

• Contain peptidoglycan and beta-lactamase

• Gram- only

Flagellum: Protein tail

Pilum/Fimbria: Glycoprotein appendage

Endospores: Form spores

• Gram+ only

Bacteria Classification

Gram staining

Shape

O2 requirements

Spore formation

Bacteria Classification: Gram Staining

Identifying cell wall

Gram+: Purple

• Cell wall trap iodine/crystal violet stain

Gram-: Pink

• No cell wall trap crystal violet stain (eluted with alcohol)

Bacteria Classification: Shape

Cocci: Sphere

• Most gram+

Bacilli: Rod

• Most gram-

Vibro: Curved

Spirilla: Spiral

Bacteria Classification: O2 Requirements

Obligate Aerobes: Require O2

Facultative Anaerobes: Can use O2 or not

Obligate Anaerobes: Harmed by O2

Aerotolerant Anaerobes: Tolerate O2 but cannot use

Microaerophiles: Require low conc O2

Bacteria Classification: Spore Formation

Endopores: Spores produced inside cell

Exospores: Spores produced outside cell

Non-Sporing: No spore production

Antibiotics

Treat bacterial infections

Indications:

• Clear bacterial etiology

• NOT for acute cough, bronchitis, sore throat

Overprescription increase MDR risk

Innate Immune System

Broad, non-specific response

Innate: Granulocytes

Neutrophils: WBC

Eosinophils: WBC

Basophils

Granulocytes: Neutrophils

Recognize antigens

Phagocytic

Produce bactericides (AMPs) → Cytotoxic

Granulocytes: Eosinophils

Secrete proinflammatory cytokines

Activate mast cells

Secrete anti-pathogen proteins (AMPs)

Granulocytes: Basophils

Produce histamine and heparin (prevent blood clot)

Innate: Natural Killer (NK) Cells

Lymphocyte detecting MHC class I (pathogenic host cells)

Cytotoxic: Release cytokines for cell lysis

Innate: Mast Cells

In interstitial connective tissue

Receptors for Fc portion of IgE antibodies

Allergen contact = IgE degranulate cell for histamine secretion and inflammation

Innate: Antigen-Presenting Cells (APCs)

Present surface peptides via MHC class I and II

APC: Monocytes

Differentiate into macrophages

Activate adaptive immune system

APC: Macrophages

Phagocytic

APC: Dendritic Cells

Express MHC class I and II + Fc receptors

Activate adaptive immune system

Phagocytic

Adaptive Immune System

Delayed, specific response

Adaptive: T-Cells

Cell-mediated response

Express antigen-specific T-cell receptors (TCR) to recognize antigen fragment presented on MHC on APCs

• Cytotoxic T-cell (MHC I) → Detect intracellular (viruses)

• Helper T-cell (MHC II) → Detect extracellular (bacteria)

Adaptive: B-Cells

Humoural response

Produce antigen-specific antibodies

URT Defense Mechanisms

Physical barriers

Chemical barriers

Biological/cellular barriers

Physical Barriers: Epithelial Cells

Prevent pathogen entry into submucosa

Smoking disrupts cell barrier

Physical Barrier: Mucus

Secreted by epithelial cells

Trap and remove pathogens via mucociliary escalator

• Winter/smoking = More dry = Less efficient

Cilia sweep mucus towards pharynx and mouth for swallowing/expectorating

Chemical Barriers: Antimicrobial Peptides (AMPs)

Secreted by neutrophils and epithelial cells

• Defensins: Chemotactic

• Lactoferrin: Modulate inflammatory cytokine production

Biological Barriers: Respiratory Tract Microbiota

Resident symbiotic organisms in resp tract

Prevent pathogen entry

Smoking/drugs = Dysbiosis = Increase infections

Biological Barrier: Innate Immune Cells

Inflammation

Phagocytosis

Lymphatic System: Transport antigens and APCs from mucosa to lymph nodes for adaptive immune activation

• Swelling from immune cell proliferation

URT Viral Infections: Manifestation

More common

Signs:

• Nasal congestion

• Cough

• Sneezing

• Sore throat

• Low-grade fever

URT Viral Infections: Transmission

Droplets: Large particles, short-range

Aerosols: Fine particles, long and short-range

Direct Contact: Short-range

Indirect Contact: Fomites, long and short-range

URT Viral Infections: Pathogenesis

Rhinovirus:

• Replicate in posterior nasopharynx epithelial cells

• Short incubation

Influenza:

• Replicate in tracheobronchial epithelial cells

• More damage

URT Viral Infections: Treatment/Management

NO antibiotics

Self-limiting

Supportive Measures:

• Rest, hydrate

• NSAIDS/acetaminophen for pain

• Antihistamines/decongestants

URT Bacterial Infections: Manifestations

Similar to viral

Differences:

• Persistent symptoms (> 10 days)

• Severe onset (high fever, prolonged nasal discharge)

• Worsening symptoms after improving (double-sickening)

URT Bacterial Infections: Transmission

Opportunistic → Dysbiosis

URT Bacterial Infections: Pathogenesis

Secondary infection after viral infection

• Inflammation

• Decrease tissue O2

Bacteria colonize mucosal surfaces to impair microbiota

URT Bacterial Infections: Treatment/Management

Antibiotics

Symptom management same as viral

Common Cold Viruses

Rhinovirus (most common)

Influenza

Parainfluenza

Coronavirus

Adenovirus

Respiratory syncytial virus

Common Cold: Rhinovirus

Inactivated by gastric acid

• Infection limited to nasopharynx + resp epithelium

Group A Streptococcal (GAS) Pharyngitis: Description

Sore throat from pharynx inflammation (strep throat)

• Fever

• Enlarged tonsils + exudate

GAS Pharyngitis: Epidemiology

Most common strep throat cause (in children)

GAS Pharyngitis: Etiology

Group A beta-hemolytic Streptococcus

• Streptococcus pyogenes

GAS Pharyngitis: Pathogenesis

Evade immune system with:

• Virulence factors (prevent phagocytosis)

• Toxin production

• Adaptive mechanisms: Pili adhere to pharyngeal epithelium, antibiotic resistance

GAS Pharyngitis: Investigation

Not needed unless high risk

• Rapid antigen detection test

• Throat culture

• Nucleic acid amplification test (ex: PCR)

GAS Pharyngitis: Clinical Presentation

Differentiate viral and bacterial pharyngitis

Centor Score:

• +1 for each criteria

  • Fever

  • Tonsil exudate

  • Lymph node swelling

  • No cough

• +1 point for < 15 years

• -1 point for > 45 years

0-1 Points: Low risk

3-4 Points: Increased risk

GAS Pharyngitis: Treatment/Management

Usually self-limiting

Supportive Care:

• Fluid

• Analgesics

Antibiotics if lab confirmed

• Penicillin

• Amoxicillin

GAS Pharyngitis: Complication of Not Treating

Acute rheumatic fever

Autoimmune reaction causing carditis (heart inflammation) and arthritis

Infection Causing Airway Obstruction

Mostly from self-limiting viral laryngotracheobronchitis

• Edema

• Pus in abscess (dead + alive immune cells) → Must drain

Infection Causing Airway Obstruction: In Children

Common

Narrow subglottic + epiglottic regions

Soft cartilage

Infection Causing Airway Obstruction: In Adults

Glottic region

Cough Indication of Location

URT/Extrathoracic:

• Barky/hoarse cough

• Stridor

• Voice hoarseness

LRT/Intrathoracic

• Dry or productive cough

• Wheezing

• More persistent