Anatomical Differences Between the Upper and Lower Respiratory Tract
The respiratory system is divided into two main regions: the upper respiratory tract and the lower respiratory tract, each with distinct anatomical features and functions.
Upper Respiratory Tract
- Anatomy: The upper respiratory tract includes the nasal cavity, sinuses, pharynx (nasopharynx, oropharynx, laryngopharynx), and larynx (above the epiglottis). It is in direct contact with the external environment.
- Functions: Its primary role is to filter, warm, and humidify incoming air. Structures like nasal hairs trap large particles, while mucus secreted by goblet cells captures smaller particles and microbes.
- Defenses: The mucociliary escalator mechanism propels trapped pathogens upward for expulsion or swallowing. Mucosa-associated lymphoid tissue (MALT), including tonsils and adenoids, provides immune surveillance.
- Normal Flora: The upper respiratory tract harbors a diverse microbiota. Common organisms include Staphylococcus epidermidis, viridans group streptococci (VGS), Corynebacterium spp., Haemophilus spp., and occasionally potential pathogens like Staphylococcus aureus.
Lower Respiratory Tract
- Anatomy: The lower respiratory tract begins below the epiglottis and includes the trachea, bronchi, bronchioles, and alveoli within the lungs. Gas exchange occurs in alveoli surrounded by capillaries.
- Functions: Its primary role is gas exchange—oxygen intake and carbon dioxide removal.
- Defenses: Alveolar macrophages are critical for engulfing pathogens that bypass upper defenses. The pleural membrane protects lung tissues during respiration.
- Normal Flora: Unlike the upper tract, the lower respiratory tract has minimal microbial colonization due to robust defenses. Transient bacteria like Pseudomonas, Streptococcus, and Prevotella may be present.
Normal Flora and Pathogens of the Respiratory Tract
Normal Flora
- The upper respiratory tract contains abundant microbiota that play roles in immune modulation and pathogen competition. Examples include:
- Staphylococcus epidermidis
- Viridans group streptococci (VGS)
- Corynebacterium spp.
- Propionibacterium spp.
- Haemophilus spp.
Pathogens
Pathogens can infect either region of the respiratory system:
- Upper Respiratory Pathogens:
- Streptococcus pyogenes (Group A Streptococcus)
- Haemophilus influenzae
- Rhinoviruses (common cold)
- Coronaviruses
- Lower Respiratory Pathogens:
- Mycobacterium tuberculosis
- Influenza virus
- Respiratory syncytial virus (RSV)
- Bacteria causing pneumonia such as Streptococcus pneumoniae, Haemophilus influenzae, or atypical agents like Mycoplasma pneumoniae.
Group A Beta-Hemolytic Streptococcus (GAS): Structure, Virulence Factors, Pathogenesis, Laboratory Diagnosis
Structure
Group A beta-hemolytic streptococcus (Streptococcus pyogenes) is a gram-positive coccus arranged in chains. It exhibits beta hemolysis on blood agar due to complete red blood cell lysis.
Virulence Factors
- M Protein: Prevents phagocytosis by interfering with opsonization; also implicated in autoimmune responses leading to sequelae like rheumatic fever.
- Hyaluronidase: Degrades connective tissue for bacterial spread.
- Streptokinase: Dissolves clots to facilitate dissemination.
- Exotoxins:
- Streptolysins O and S destroy red/white blood cells.
- Pyrogenic exotoxins act as superantigens causing toxic shock-like syndrome.
Pathogenesis
S. pyogenes causes infections primarily through direct invasion of tissues or toxin-mediated damage:
- Adheres to epithelial cells via M protein.
- Produces enzymes/toxins that degrade host tissues or trigger excessive immune responses.
Laboratory Diagnosis
- Rapid antigen detection tests (RADTs) detect Group A carbohydrate antigens but may yield false negatives (~30%).
- Culture remains gold standard—beta hemolysis on blood agar confirms diagnosis.
- Gram staining reveals gram-positive cocci in chains.
Diseases Caused by Group A Streptococcus
Common Diseases
- Pharyngitis (Strep Throat):
- Symptoms: Fever >38°C, sore throat, swollen tonsils with pus patches.
- Epidemiology: Spread via droplets; common among children aged 5–15 years.
- Scarlet Fever:
- Caused by strains producing pyrogenic exotoxins; presents with a characteristic rash.
- Skin Infections:
- Impetigo or erysipelas caused by localized infection.
- Invasive Infections:
- Necrotizing fasciitis (“flesh-eating disease”).
- Streptococcal toxic shock syndrome due to superantigen activity.
- Post-Infectious Sequelae:
- Acute rheumatic fever from molecular mimicry between M protein and heart tissue.
- Acute glomerulonephritis due to immune complex deposition in kidneys.
Treatment and Prevention
Treatment
- First-line antibiotics include penicillin G or amoxicillin; resistance is rare for GAS.
- For penicillin-allergic patients, macrolides like azithromycin are alternatives.
Prevention
Preventive measures include good hygiene practices such as handwashing to reduce transmission.
Why There Is No Vaccine for Group A Streptococcus
Despite decades of research efforts, no vaccine exists for GAS due to several challenges:
- High variability of M protein serotypes complicates broad vaccine coverage development.
- Concerns about triggering autoimmune reactions (e.g., rheumatic fever) because of molecular mimicry between M protein epitopes and human tissues.
- Limited understanding of long-term immunity against GAS infections hampers vaccine design.
The anatomical differences between the upper and lower respiratory tracts influence their respective defenses against pathogens as well as their normal flora composition. Group A beta-hemolytic streptococcus (S. pyogenes) remains a significant pathogen responsible for various diseases ranging from mild pharyngitis to life-threatening invasive infections or post-infectious sequelae like rheumatic fever or glomerulonephritis.
While effective treatments exist using antibiotics such as penicillin G or amoxicillin, vaccine development faces substantial hurdles due to antigenic diversity of virulence factors like M protein alongside concerns about autoimmunity triggered by molecular mimicry.
Morphology and Structure of Haemophilus influenzae
Haemophilus influenzae is a small, pleomorphic, Gram-negative coccobacillus. Its dimensions are approximately 1 µm in length and 0.3 µm in width. The bacterium is non-motile, non-spore-forming, and facultatively anaerobic. It is fastidious in nature, requiring specific growth factors for survival: hemin (factor X) and nicotinamide adenine dinucleotide (NAD or factor V). These requirements explain its name “Haemophilus,” which means “blood-loving.”
The bacterium can be classified into two major groups based on the presence or absence of a polysaccharide capsule:
- Encapsulated strains: These possess a polysaccharide capsule and are further divided into six serotypes (a through f). Among these, type b (H. influenzae type b or Hib) is the most virulent.
- Nonencapsulated strains: Known as nontypeable H. influenzae (NTHi), these lack a capsule and are genetically diverse.
The encapsulated strains have an antiphagocytic capsule composed of polyribosyl ribitol phosphate (PRP), which plays a critical role in their virulence by helping them evade host immune responses.
Growth and Pathogenesis
Growth
H. influenzae grows best at temperatures between 35°C and 37°C under capnophilic conditions (requiring increased CO₂ levels). It requires enriched media such as chocolate agar because it depends on factor X (hemin) and factor V (NAD) for growth. These factors are released from lysed red blood cells during preparation of chocolate agar.
Pathogenesis
The pathogenesis of H. influenzae involves several steps:
- Colonization: The bacteria typically colonize the nasopharynx asymptomatically in many individuals.
- Invasion: Encapsulated strains can invade mucosal surfaces, enter the bloodstream, and disseminate to sterile sites such as the meninges, joints, or lungs.
- Virulence Factors:
- The polysaccharide capsule prevents phagocytosis by immune cells.
- Lipooligosaccharides (LOS) on the bacterial surface contribute to adhesion to epithelial cells and evasion of complement-mediated killing.
- NTHi strains form biofilms that enhance persistence in chronic infections like otitis media or bronchitis.
Immunity, Transmission, and Epidemiology
Immunity
Immunity against H. influenzae, particularly Hib, relies heavily on antibodies directed against the PRP capsule. Newborns initially have some protection due to maternal antibodies transferred transplacentally; however, this wanes within months after birth. Vaccination with the Hib conjugate vaccine induces robust immunity by stimulating antibody production against PRP.
Transmission
Transmission occurs via respiratory droplets from person to person through coughing or sneezing. Close contact with carriers or infected individuals increases the risk of spread.
Epidemiology
Before widespread vaccination programs began in the late 1980s, Hib was a leading cause of invasive diseases such as meningitis among children under five years old. With vaccination efforts:
- The incidence of invasive Hib disease has decreased by over 99% in developed countries.
- Non-typeable H. influenzae now accounts for most invasive infections across all age groups.
Populations at higher risk include unvaccinated children, immunocompromised individuals (e.g., those with HIV), people with asplenia or sickle cell disease, American Indians/Alaska Natives, and adults over 65 years old.
Types of Haemophilus influenzae Infections
Infections caused by H. influenzae can range from mild to severe:
- Encapsulated Strains (Hib):
- Meningitis: A life-threatening infection causing inflammation of the brain’s protective membranes.
- Epiglottitis: Swelling of the epiglottis leading to airway obstruction.
- Pneumonia: Lung infection often presenting with fever, cough, and difficulty breathing.
- Septic arthritis: Infection of joints causing pain and swelling.
- Cellulitis: Skin infection commonly affecting facial regions like cheeks or around the eyes.
- Non-Typeable Strains (NTHi):
- Otitis media: Middle ear infections common in children.
- Sinusitis: Inflammation/infection of sinuses.
- Bronchitis: Particularly exacerbations in patients with chronic obstructive pulmonary disease (COPD).
- Rarely causes invasive diseases but may lead to bacteremia or pneumonia in immunocompromised individuals.
Laboratory Diagnosis
Diagnosis involves identifying H. influenzae using clinical samples such as blood, cerebrospinal fluid (CSF), sputum, or middle ear aspirates:
- Microscopy:
- Gram staining reveals Gram-negative coccobacilli.
- Culture:
- Requires chocolate agar supplemented with factors X and V for growth.
- Colonies appear smooth and grayish.
- Serotyping:
- Slide agglutination tests using type-specific antisera help identify encapsulated strains.
- Molecular Techniques:
- Polymerase chain reaction (PCR) can detect capsular genes for precise identification.
- Other Tests:
- Latex particle agglutination tests can rapidly detect PRP antigen in CSF during suspected meningitis cases.
Treatment and Prevention
Treatment
Treatment depends on the severity of infection but generally includes antibiotics effective against H. influenzae. Common options include:
- Third-generation cephalosporins like ceftriaxone or cefotaxime for severe invasive infections such as meningitis.
- Amoxicillin-clavulanic acid for mild infections like otitis media or sinusitis caused by NTHi strains.
- Rifampin prophylaxis may be recommended for close contacts during outbreaks involving Hib cases.
Resistance to antibiotics like ampicillin due to beta-lactamase production is common among both encapsulated and non-typeable strains.
Prevention
Vaccination remains the cornerstone for preventing Hib infections:
- The Hib conjugate vaccine is administered routinely during infancy starting at two months old.
- Booster doses ensure long-term immunity.
For non-typeable infections caused by NTHi strains, no vaccines currently exist due to their genetic diversity; preventive measures focus on hygiene practices like handwashing.
