Microbial Diseases of the Respiratory System

Microbial Diseases of the Respiratory System

Reading & Assignments

  • Lecture 19: Microbial diseases of the respiratory system, Chapter 24
  • Lecture 20: Microbial diseases of the nervous system, Chapter 22

Upcoming Labs

  • Lab 21: Identification of an unknown bacterium
    • Gram stain
    • Cultural isolation
    • Biochemical testing
    • Antibiotic resistance
    • Lab report

Lecture Learning Objectives

  • Describe the structure of the respiratory system and the mechanisms that protect the upper and lower respiratory systems from infection.
  • Describe the differences between the strains of Streptococcus pyogenes that cause strep throat and scarlet fever.
  • Name the organism that causes diphtheria and describe the typical symptoms associated with this illness.
  • Name microorganisms commonly associated with otitis media.
  • Describe the symptoms and treatment of the common cold and name two types of viruses that can cause this illness.
  • Name the organism that causes whooping cough and describe its virulence factors.
  • Describe the symptom progression of whooping cough.
  • Describe the symptoms and progression of tuberculosis.
  • Describe the methods used to diagnose tuberculosis and the pros and cons of each.
  • Describe the symptoms of pneumonia.
  • Name and describe the major features of different microbes that can cause pneumonia.
  • Describe the symptoms of influenza and respiratory syncytial virus.
  • Define the terms antigenic drift and antigenic shift.
  • Describe how antigenic shift and drift contribute to the need for new influenza vaccines each year.

The Lower Respiratory System

  • Larynx
  • Trachea
  • Lungs
  • Bronchial tubes
  • Alveoli
  • No resident microflora

The Upper Respiratory System

  • Nose
  • Pharynx
  • Middle ear
  • Eustachian tubes
  • Normal microflora
    • May include potential pathogens
    • Helps to prevent infection
    • IgA antibodies in mucus, saliva, tears provide protection

Streptococcal Pharyngitis (Strep Throat)

  • Group A streptococci
    • Streptococcus pyogenes
    • Gram-positive cocci in chains
    • Pharyngitis
    • Tonsillitis
    • Enlarged lymph nodes
  • Resistant to phagocytosis
  • Enzymes
    • Streptokinase – destroys blood clots
    • Streptolysins – cytotoxic
  • Rapid antigen detection
    • Latex agglutination
    • Enzyme immunoassay
  • Treatment with penicillin or penicillin derivatives

Scarlet Fever

  • Group A streptococci
    • Streptococcus pyogenes
  • Erythrogenic toxin (acquired from bacteriophage)
  • Pink/red skin rash – reaction to toxin
  • High fever
  • Spotted tongue

Diphtheria

  • Corynebacterium diphtheriae
    • Gram-positive rod
    • Non-endospore-forming
  • Exotoxin (acquired from bacteriophage)
  • Difficult to diagnose
  • Antitoxin treatment (antibodies to neutralize the toxin)
  • DTaP vaccine (toxoid) – Artificially acquired
  • Malaise
  • Swelling of the neck
  • Membrane formation in the throat
  • Suffocation

Otitis Media

  • Streptococcus pneumoniae (35%)
  • Haemophilus influenzae (20-30%)
  • Moraxella catarrhalis (10-15%)
  • Streptococcus pyogenes (8-10%)
  • Staphylococcus aureus (1-2%)
  • No bacteria isolated (3-5%)
  • Most frequent in children
    • Smaller and more horizontal Eustachian tube
  • Pus buildup from infection puts pressure on the eardrum
  • Eardrum becomes inflamed
  • May be treated with antibiotics

The Common Cold

  • >200 different viruses
    • Rhinoviruses (30-50%)
    • Coronaviruses (10-15%)
    • Unknown cause (20-30%)
  • Low infectious dose
  • Immunity acquired over time
Symptoms
  • Sneezing
  • Runny nose
  • Congestion
  • No fever
Complications
  • Otitis media – ear infection
  • Laryngitis – inflammation of the voice box
Treatments
  • Medications can ease symptoms but do not speed recovery
  • Cough suppressants
  • Decongestants
  • Infection usually clears in about 1 week

The Lower Respiratory System (Protection)

  • Larynx
  • Trachea
  • Lungs
  • Bronchial tubes
  • Alveoli
  • Ciliary escalator
  • Alveolar macrophages
  • IgA antibodies on mucosal surfaces
  • NO resident microflora

Pertussis (Whooping Cough)

  • Bordetella pertussis
    • Gram-negative
    • Coccobacillus
    • Obligate aerobe
    • Virulent strains produce a capsule
Virulence Factors
  • Attach to ciliated cells in trachea
  • Toxin production
    • Tracheal cytotoxin – damages ciliated cells
    • Pertussis toxin – enters bloodstream to cause systemic symptoms
Disease progression
  • Catarrhal stage: Common cold
  • Paroxysmal stage: Damage to tracheal cells stops the ciliary escalator, prolonged coughing spells, accumulation of mucus
  • Convalescence stage: Persistent cough (months), susceptible to secondary infections
Diagnosis
  • Clinical signs and symptoms
  • Bacteria are difficult to grow in the lab
  • DNA-based identification methods
Treatment & prevention
  • Antibiotics – erythromycin
  • Part of the DTaP vaccine (subunit)

Tuberculosis (TB)

  • Mycobacterium tuberculosis
    • Rod-shaped
    • Obligate aerobe
    • Acid-fast
    • Slow growth (generation time of ~20 hours)
    • Low infectious dose (1-3 cells in the lungs)
Symptoms
  • Coughing
  • Bloody sputum
  • Weight loss
  • Loss of vigor
Global Impact
  • Estimated 10.6 million people fell ill with tuberculosis in 2022
  • Testing and treatment may not be accessible in areas where the disease is more prevalent
Pathogenesis
  1. Bacteria enter lungs
  2. Tubercule formation
    • Bacteria multiply in macrophages
    • Cytokines released
    • Macrophages surround bacteria
    • Inflammation damages lung tissue
  3. Caseous center formation
    • Macrophages die and release bacteria
    • Symptoms appear
    • Bacteria may remain dormant (latent TB)
    • Disease may be arrested  lesions become calcified
  4. Mature tubercule formation
    • Caseous center enlarges and fills with air
    • Bacteria can now multiply outside of macrophages
  5. Tubercule ruptures
    • Bacteria are released
    • Spread to circulatory and lymphatic systems
Diagnosis
  • Tuberculin skin test
    • Purified TB toxin injected under the skin
    • Observe for an immune response
    • Does the immune system recognize and respond to the toxin?
  • X-ray or CT scan (lungs)
  • Isolation of bacteria from sputum (3-12 weeks)
  • Nucleic acid amplification
    • Can identify infection faster, but cannot distinguish active and latent infections
    • Can also test for antibiotic resistance
Treatment
  • First line drugs
    • Isoniazid – fatty acid synthesis
    • Ethambutol – cell wall formation
    • Rifampin – RNA synthesis
    • Pyrazinamide – unknown mechanism
  • MDR – multi-drug resistant TB is resistant to both isoniazid and rifampin
  • Second line drugs
    • Aminoglycosides – protein synthesis
    • Fluoroquinolones – nucleic acid synthesis
    • Para-aminosalicylic acid – inhibits folate synthesis
  • XDR – extensively drug resistant TB is resistant to fluoroquinolones and at least one other 2nd line drug
Vaccine
  • BCG vaccine (live attenuated)
  • Not commonly administered in USA due to low incidence rates
  • Recommended for children at high risk with a negative skin test
  • Not effective for adults
  • Children with HIV can develop a fatal infection from the vaccine
  • False positive skin test

Pneumonia

  • Inflammation and fluid build-up in the lungs
  • Can be bacterial, viral, or fungal
Bacterial Pneumonia
  • Streptococcus pneumoniae
    • Gram-positive
    • Ovoid
    • Capsule – resistance to phagocytosis
    • Symptoms: High fever, difficulty breathing, chest pain, bloody sputum
    • Diagnosis: Cultural isolation, urine test (antigen detection)
    • Treatment with antibiotics: Penicillin resistance
  • Legionella pneumophila
    • Gram-negative
    • Rod-shaped
    • Associated with contaminated water
    • Diagnosis: Cultural isolation, fluorescent antibody methods, DNA probe test
  • Chlamydia psittaci
    • Gram-negative
    • Rod-shaped
    • Obligate intracellular pathogen
    • Elementary bodies – can survive but not reproduce outside the host
    • Spread though contact with bird droppings
    • Diagnosis: Serology – difficult due to antigenic variation
  • Coxiella burnetii (Q fever)
    • Gram-negative
    • Rod-shaped
    • Obligate intracellular pathogen
    • Endospore-like structure – heat resistant
    • Low infectious dose (1 cell)
    • Exposure on farms or in dairy and meat products
    • Diagnosis: Cell culture, serology
  • Mycoplasma pneumoniae (walking pneumonia)
    • No cell wall
    • Produce tiny fried egg colonies
    • Symptoms persist for 3+ weeks: Low fever, cough, headache
    • Diagnosis & treatment: Bacterial culture can take up to 3 weeks, rapid PCR tests, usually treated with tetracyclines
Pneumocystis Pneumonia
  • Pneumocystis jirovecii
    • Fungus (or protozoan)
    • Sexual reproduction
    • Immunocompromised patients: Infants, AIDS patients
    • Healthy adults usually have few to no symptoms
Viral Pneumonia
  • Complication from a viral infection
    • Influenza
    • Measles
    • Chicken pox
    • Severe Acute Respiratory Syndrome (SARS)
    • SARS-associated coronavirus (2003)
    • Middle East Respiratory Syndrome
    • MERS coronavirus (2012)

COVID-19

  • SARS-CoV2 – novel coronavirus first identified in 2019
  • COVID-19 – coronavirus disease 2019
    • Symptoms: Fever, cough, shortness of breath or difficulty breathing, chills, repeated shaking with chills, muscle pain, headache, sore throat, loss of taste or smell
    • Can be fatal
    • 1.2% case fatality in US

Long COVID

  • New, returning, or ongoing health problems experienced 4 or more weeks after being first infected
  • At least 7.5% of adults develop long COVID after recovering from the initial illness
    • Symptoms: Difficulty breathing, tiredness/fatigue, post-exertional malaise, “Brain fog”, cough, chest or stomach pain, headache, heart palpitations, joint or muscle pain, diarrhea, sleep problems, fever, lightheadedness, rash, mood changes, change in smell or taste, change in menstrual cycles
    • Multi-organ effects (heart, lungs, kidneys, skin, brain)
    • Autoimmune conditions
Transmission
  • Aerosol transmission
    • Aerosols (very small droplets) containing virus are expelled and may remain in the air
    • May also spread through droplets on surfaces (uncommon)
  • Incubation period: 4-6 days; up to 14 days
  • Pre-symptomatic carriers
    • Most infectious 2-3 days before symptoms appear
SARS-COV2 Variants
  • New variants
    • Virus can only mutate when it replicates (no proofreading mechanism)
    • Many mutations in spike protein
    • Antigenic changes could reduce immune protection
    • Fewer infections  fewer new variants

Influenza

Symptoms
  • Chills
  • Fever
  • Headache
  • Muscle aches
  • 3,000 – 50,000 people die in the US each year
Influenzavirus
  • Helical
  • Enveloped
  • Segmented RNA genome
  • Spikes – virus recognizes host cell
    • Hemagglutinin (HA) – attachment to host cells; clumping of RBC
    • Neuraminidase (NA) – viral release
Vaccine
  • Inactivated vaccine produced in eggs or cell culture
    • Takes several months to produce
    • Does not protect against all strains of the flu
  • Hemagglutinin (H)
  • Neuraminidase (N)
  • New vaccines required each year because viral antigens have changed
Antigenic drift
  • Slow accumulation of genetic mutations that alter the antigens on the surface of the virus
  • No proofreading mechanism for viral RNA
  • Antigenic drift over time allows viruses to evade the host immune system
Antigenic shift
  • Shuffling of segmented viral genome
  • Causes large, rapid changes in viral antigens
  • Host cell is infected by multiple strains of the virus
  • Different RNA segments may be packaged together
  • New combinations of antigens
  • May allow virus to infect other organisms
  • Evade immune system

Respiratory Syncytial Virus (RSV)

  • Enveloped, single-stranded RNA virus
  • Causes formation of syncytia
  • Mutates quickly
  • Naturally acquired immunity is weak
  • Reinfection is possible
  • Most children have been infected by age 2
  • Causes coughing and wheezing (more than 1 week)
  • Most common cause of viral respiratory disease in infants
  • Can cause pneumonia in older adults
Occurrence
  • Usually seasonal
    • Winter/early spring
  • Increased infections earlier in the 2022 season
  • Delayed exposure to virus due to pandemic lockdowns and mask usage

Suggested Study Questions

  • Chapter 24
    • Knowledge and comprehension
    • Review: 4, (streptococcal pharyngitis, scarlet fever, diphtheria, whooping cough, tuberculosis, pneumococcal pneumonia, H. influenza pneumonia, chlamydial pneumonia, otitis media) 6, 8, 10
    • Multiple choice: 2, 9, 10
    • Analysis: 1, 2, 3