Microbial Diseases of the Respiratory System

Structure and Function of the Respiratory System

The respiratory system is divided into upper and lower regions, each with distinct anatomical features and defense mechanisms against microbial invasion.

• Upper respiratory system: Includes the nose, pharynx, middle ear, and eustachian tubes. - and tears contain antimicrobial substances that protect mucosal surfaces.

• Lower respiratory system: Comprises the larynx, trachea, bronchial tubes, and alveoli. - The ciliary escalator moves particles toward the throat via ciliary action. - Alveolar macrophages destroy microorganisms in the lungs. - Respiratory mucus traps and removes pathogens.

Example: The ciliary escalator is a key defense, as ciliated epithelial cells sweep mucus and trapped microbes upward toward the throat for expulsion.

Normal Microbiota of the Respiratory System

The upper respiratory tract hosts a diverse microbiota that plays a protective role, while the lower respiratory tract is nearly sterile under normal conditions.

• Normal microbiota: Suppress pathogens by competing for nutrients and producing inhibitory substances.

• Lower respiratory system: Nearly sterile due to effective host defenses.

Example: Streptococcus species in the upper respiratory tract can inhibit the growth of pathogenic bacteria.

Microbial Diseases of the Upper Respiratory System

Common Infections and Their Features

Several diseases affect the upper respiratory tract, each with distinct symptoms and clinical significance.

• Pharyngitis: Inflammation of the pharynx, commonly presenting as a sore throat.

• Laryngitis: Inflammation of the larynx, often resulting in hoarseness.

• Tonsillitis: Inflammation of the tonsils, may cause difficulty swallowing.

• Sinusitis: Inflammation of the sinuses, usually self-limiting.

• Epiglottitis: Severe inflammation of the epiglottis; most life-threatening among upper respiratory diseases.

Bacterial Diseases of the Upper Respiratory System

Several bacterial pathogens cause significant diseases in the upper respiratory tract, with varying symptoms, treatments, and diagnostic methods.

• Streptococcal pharyngitis (strep throat): - Causative agent: Group A streptococci (Streptococcus pyogenes) - Virulence factors: Resistant to phagocytosis, streptokinases (lyse clots), streptolysins (cytotoxic) - Symptoms: Local inflammation, fever, tonsillitis, enlarged lymph nodes - Diagnosis: Enzyme immunoassay (EIA) tests

• Scarlet fever: - Causative agent: Lysogenized S. pyogenes - Virulence factor: Erythrogenic toxin

• Diphtheria: - Causative agent: Corynebacterium diphtheriae (Gram-positive rod, pleomorphic) - Symptoms: Tough grayish membrane in throat (fibrin and dead tissue), blocks air passage - Virulence factor: Exotoxin damages heart and kidneys - Prevention: DTaP vaccine (diphtheria toxoid)

• Cutaneous diphtheria: - Symptoms: Skin ulcer formation

• Otitis media: - Infection of the middle ear - Symptoms: Pus formation, pressure on eardrum - Common causes:

  • Streptococcus pneumoniae (35%)

  • Nonencapsulated Haemophilus influenzae (20–30%)

  • Moraxella catarrhalis (10–15%)

  • S. pyogenes (8–10%)

  • Staphylococcus aureus (1–2%)

  Treatment: Broad-spectrum penicillins

Diseases in Focus 24.1: Summary Table

Viral Disease of the Upper Respiratory System

The common cold is a viral infection with numerous causative agents and no specific cure.

• Causative agents: Over 200 viruses, mainly rhinoviruses (30–50%) and coronaviruses (10–15%)

• Symptoms: Sneezing, nasal secretion, congestion; may lead to laryngitis and otitis media; not accompanied by fever

• Treatment: Symptomatic relief (cough suppressants, antihistamines); antibiotics are ineffective

Bacterial Diseases of the Lower Respiratory System

Overview and Common Conditions

Lower respiratory infections are often more severe and can involve the pulmonary alveoli.

• Bronchitis: Inflammation of the bronchi

• Bronchiolitis: Inflammation of the bronchioles

• Pneumonia: Infection involving the alveoli

Pertussis (Whooping Cough)

Pertussis is a highly contagious bacterial disease affecting the lower respiratory tract.

• Causative agent: Bordetella pertussis (Gram-negative coccobacillus)

• Virulence factors: Capsule (attachment to ciliated cells), tracheal cytotoxin (damages ciliated cells), pertussis toxin (systemic effects)

• Stages:

  1. Catarrhal stage: mild, cold-like symptoms

  2. Paroxysmal stage: violent coughing, gasping for air

  3. Convalescence stage: recovery, may last for months

• Prevention: DTaP vaccine

• Treatment: Erythromycin or other macrolides

Tuberculosis

Tuberculosis is a chronic bacterial infection with global health significance.

• Causative agent: Mycobacterium tuberculosis (acid-fast rod, obligate aerobe)

• Other causes: Mycobacterium bovis (bovine TB), Mycobacterium avium-intracellulare (HIV patients)

• Pathogenesis:

  • Inhaled organisms phagocytized by alveolar macrophages

  • Mycolic acids stimulate inflammatory response

  • Organisms isolated in tubercles, which may calcify (Ghon's complexes)

  • Tubercles may break down, releasing bacteria (miliary TB)

• Diagnosis: Tuberculin skin test, X-ray/CT, acid-fast staining, culture, rapid blood tests (IFN-γ, PCR)

• Treatment:

  • Minimum 6 months drug therapy

  • First-line drugs: isoniazid, ethambutol, pyrazinamide, rifampin

  • Second-line drugs: aminoglycosides, fluoroquinolones, PAS

  • MDR and XDR strains require alternative regimens

• Prevention: BCG vaccine (live avirulent M. bovis), not widely used in the US

Example: Tuberculin skin test involves intradermal injection of purified protein derivative; induration indicates exposure.

Bacterial Pneumonias

Pneumonia is classified based on causative agents and affected lung regions.

• Typical pneumonia: Caused by S. pneumoniae

• Atypical pneumonia: Caused by other microorganisms

• Lobar pneumonia: Infects lobes of the lungs

• Bronchopneumonia: Infects alveoli adjacent to lungs

• Pleurisy: Inflammation of pleural membranes

Pneumococcal Pneumonia

• Causative agent: Streptococcus pneumoniae (Gram-positive, encapsulated diplococci)

• Symptoms: Alveoli fill with fluids and RBCs, impaired oxygen uptake

• Diagnosis: Optochin-inhibition test, bile solubility test, antigen in urine

• Treatment: Macrolides, fluoroquinolones

• Prevention: Conjugated pneumococcal vaccine

Haemophilus influenzae Pneumonia

• Causative agent: Haemophilus influenzae (Gram-negative coccobacillus)

• Predisposing factors: Alcoholism, poor nutrition, cancer, diabetes

• Symptoms: Similar to pneumococcal pneumonia

• Diagnosis: Isolation on special media (X and V factors)

• Treatment: Cephalosporins

Mycoplasmal Pneumonia

• Causative agent: Mycoplasma pneumoniae (no cell wall)

• Symptoms: Mild but persistent, low fever, cough, headache

• Diagnosis: "Fried-egg" appearance on media

• Treatment: Tetracyclines

Legionellosis (Legionnaires' Disease)

• Causative agent: Legionella pneumophila (aerobic, Gram-negative rod)

• Transmission: Inhalation of aerosols; not person-to-person

• Symptoms: High fever, cough (similar to Pontiac fever)

• Treatment: Erythromycin, macrolides

Chlamydial Pneumonia

• Causative agent: Chlamydophila pneumoniae

• Transmission: Person-to-person

• Symptoms: Mild respiratory illness, resembles mycoplasmal pneumonia

• Diagnosis: Serological tests

• Treatment: Tetracyclines

Psittacosis (Ornithosis)

• Causative agent: Chlamydophila psittaci (Gram-negative intracellular bacterium)

• Transmission: Bird droppings, airborne elementary bodies

• Symptoms: Fever, headache, chills, disorientation

• Diagnosis: Growth in eggs, cell culture, PCR

• Treatment: Tetracyclines

Q Fever

• Causative agent: Coxiella burnetii (obligate intracellular gammaproteobacteria)

• Transmission: Tick bites (animals), inhalation of aerosols, unpasteurized milk (humans)

• Symptoms: Acute: high fever, muscle aches, headache, coughing; Chronic: endocarditis

• Treatment: Doxycycline (acute), chloroquine (chronic)

Viral Diseases of the Lower Respiratory System

Viral Pneumonia, RSV, and Influenza

• Viral pneumonia: Often a complication of influenza, measles, or chickenpox; difficult to diagnose

• Respiratory Syncytial Virus (RSV): Most common in infants and older adults; causes cell fusion (syncytium), coughing, wheezing; diagnosed by serological tests; treated with palivizumab

• Influenza (Flu): - Virus: Influenzavirus (eight RNA segments, lipid bilayer) - Symptoms: Chills, fever, headache, muscle aches - Antigenic drift: Minor changes in HA and NA spikes - Antigenic shift: Major changes, reassortment of RNA segments, leads to pandemics - Prevention: Annual multivalent vaccine - Treatment: Zanamivir (Relenza), oseltamivir (Tamiflu) inhibit neuraminidase

Fungal Diseases of the Lower Respiratory System

Major Fungal Pathogens

• Histoplasmosis: Histoplasma capsulatum (dimorphic fungus); acquired from bird/bat droppings; treated with itraconazole

• Coccidioidomycosis (Valley Fever): Coccidioides immitis (dimorphic fungus); found in desert soils; treated with fluconazole or itraconazole

• Pneumocystis Pneumonia (PCP): Pneumocystis jirovecii; primary indicator of AIDS; treated with trimethoprim-sulfamethoxazole

• Blastomycosis: Blastomyces dermatitidis (dimorphic fungus); causes pneumonia and cutaneous abscesses; treated with itraconazole and amphotericin B

• Other fungi: Aspergillus fumigatus (aspergillosis), Rhizopus, Mucor; risk factors include immunocompromised state, cancer, diabetes

Big Picture: Bioterrorism and Microbial Diseases

Biological Weapons and Public Health

Microbial pathogens have been used as biological weapons throughout history, prompting international bans and modern detection strategies.

• Historical examples: Plague, smallpox, anthrax, botulinum toxin

• Modern response: Geneva Conventions, Biological Weapons Convention, rapid screening systems (DNA chips, recombinant cells, Pro Strips)

• Potential bioweapon agents:

  • Bacterial: Bacillus anthracis (anthrax), Yersinia pestis (plague), Francisella tularensis (tularemia), Vibrio cholerae (cholera), Clostridium botulinum (botulism), Chlamydophila psittaci (psittacosis)

  • Viral: Smallpox, Ebola, Marburg, Lassa, Hantavirus, Nipah virus

• Public health measures: Vaccination, rapid identification, emergency protocols

Example: The 2001 anthrax attacks in the United States highlighted the need for rapid detection and response to bioterrorism threats.