Respiratory Tract Infections: Microbial Agents & Defenses

Microbial Agents Causing Respiratory Tract Infections - Part 1

• Infants and small children with sore throats tend to develop middle ear and mastoid infections.
• Older children and adults experience more acute infections with intense pharyngitis, tonsillitis, purulent exudate, high fever, and tender cervical lymph nodes.
• Penicillin G is a treatment drug; macrolides like Erythromycin and Clindamycin can be used if allergic to Pen G.

Respiratory Tract Divisions and Defenses

• The respiratory tract divides into the upper (mouth, nose, nasal cavity, sinuses, throat, epiglottis, larynx) and lower (trachea, bronchi, bronchioles, alveoli) sections.
• Protection includes nasal hair, cilia, mucus, complement, antimicrobial peptides, cytokines, macrophages, and secretory IgA.

Respiratory Tract Infections (RTIs)

• RTIs are categorized as upper (nasal cavity, pharynx, epiglottis, larynx) or lower (trachea, bronchi, bronchioles, alveoli).
• Common Upper Respiratory Tract Infections (URTI) include common colds/rhinitis, sinusitis, acute otitis media, pharyngitis, tonsillitis, diphtheria, parotitis, acute epiglottitis, and oral cavity infections.

URTIs: Bacterial and Viral Agents

• Bacterial agents include Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Mycobacterium tuberculosis, Mycobacterium bovis, and atypical Mycobacterium.
• Viral agents encompass common cold viruses, Coronavirus, Rhinovirus, Adenovirus, Epstein-Barr virus, Influenza virus, Metapneumovirus, Parainfluenza virus, SARS-1, MERS-CoV, SARS-2, Respiratory syncytial virus, Measles, German measles, and Varicella.

URTIs: Additional Agents

• Other bacterial agents include Corynebacterium diphtheriae, Actinomycetes, Nocardia, Mycoplasma Pneumoniae, Legionella Pneumophila, Chlamydia Pneumoniae, Klebsiella, Pseudomonas, and Anaerobes.
• Fungal agents include Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Cryptococcus neoformans, Pneumocystis jeroveci, Aspergillus fumigatus, Mucor, Rhizopus and Paracoccidioides brazilienses

Bacterial Agents: Streptococcal Infections

• Includes acute pharyngitis (bacterial sore throat), streptococcal pyoderma (impetigo), erysipelas, cellulitis, necrotizing fasciitis (streptococcal gangrene), Rheumatic fever, and acute glomerulonephritis.
• Streptococcal Sore Throat (Pharyngitis): Most common infection caused by gram (+) streptococci, Group A beta-hemolytic, Catalase (-), M proteins, and ẞ-hemolysis on blood agar

Streptococcus pneumoniae (Pneumococcus)

• Gram (+) lancet-shaped diplococci with a polysaccharide capsule, requires increased CO2 for growth, and forms circular, glistening, dome-shaped colonies on blood agar.
• Optochin sensitivity is a presumptive test for Pneumococci.
• Pneumococcus is lysed by bile (positive bile solubility), unlike Viridans strep.

Pneumococcal and Viridans Streptococci Differentiation

• Streptococcus Mitis: Not lysed by bile, optochin resistant, negative Quellung reaction.
• Streptococcus pneumoniae: Lysed by bile, optochin susceptible, positive Quellung reaction.

Quellung Reaction (Neufeld-Quellung)

• Most useful and rapid method of identifying and typing Pneumococci
• Capsular swelling is the basis of serotyping due to homologous antibody binding

Streptococcus pneumoniae: Virulence Factors

• Polysaccharide capsule resists phagocytosis.
• Adherence is enabled via N-acetylglucosamine-galactose interaction.
• Enzymes: Neuraminidase destroys glycolipids/glycoproteins; Protease.
• Toxins: Pneumolysin O is cytolytic; Autolysin inhibits cell division/facilitates pneumolysin release.
• Cell wall components: Teichoic acid and peptidoglycan are activators of meningeal inflammation.

Streptococcus pneumoniae: Antigenic Structure

• Polysaccharide capsular antigens are the basis for classifying into >90 types (Quellung reaction)
• Somatic antigens include C-polysaccharide, teichoic acid, and peptidoglycan.

Streptococcus pneumoniae: Clinical Infection and Predisposing Factors

• Adults commonly affected by types 1-8. Children types 6, 14, 19, 23.
• Predisposing factors include viral and respiratory infections, mucus accumulation, bronchial obstruction, irritants, alcohol/drug intoxication, abnormal circulatory dynamics, malnutrition, debility, sickle cell anemia, hyposplenism, nephrosis, and complement deficiency.

Pneumococcal Pneumonia (Lobar Pneumonia)

• Invasion of alveolar tissue by pneumococci results in edema fluid, neutrophil and RBC accumulation.
• Leads to consolidation of a lobe, causing 60% of bacterial pneumonias; also causes otitis media, sinusitis, meningitis, and septicemia.

Pneumococcal Pneumonia: Clinical Manifestations, Diagnosis, and Treatment

• Sudden high fever/chills, pleuritic pain, productive cough with "rusty" sputum; complications include effusion, empyema, meningitis, pericarditis, endocarditis, bacteremia.
• Diagnosis: Sputum Gram stain, culture, optochin sensitivity, bile solubility, Quellung.
• Treatment: Penicillin/Vancomycin sensitive; vaccine consists of 23 serotypes for 90% of infections.

Staphylococcus aureus

• Staphylococcal pneumonia leads to abscess formation and empyema.

Haemophilus: General Characteristics

• Small, pleomorphic, gram (-) rods require blood factors (hemin and NAD).
• Species include Haemophilus influenzae, Haemophilus aegyptius, Haemophilus haemolyticus, Haemophilus ducreyi, and Haemophilus parainfluenzae.

Hemophilus influenzae (Pfeiffer Bacillus)

• Small gram (-) coccoid bacilli; encapsulated and unencapsulated; generally aerobic.
• Grown on Chocolate agar at 37°C, pH 7.4-7.8 (heat releases X and V factors); Blood agar with "Satellite phenomenon" due to V-factor release from S. aureus.

Haemophilus influenzae: Antigenic Structures and Clinical Infection

• Capsular polysaccharide is the major antigen; Serotype b is most invasive and contains ribose/ribitol phosphates (Hib vaccine).
• Enters via respiratory tract, found in tracheobronchial epithelium then bloodstream; Serotype b is most invasive.
• Susceptibility increases with IgA deficiency, sickle cell, splenectomy, chronic pulmonary infection, and alcoholism.

Haemophilus influenzae: Clinical Manifestations and Diagnosis

• Causes bacteremia, acute epiglottitis, cellulitis, meningitis, pneumonia, otitis media, pyarthrosis, pericarditis.
• Diagnosed by Gram stain, culture from blood/CSF/sputum, X/V factor testing, and antigen detection.

Haemophilus influenzae: Treatment and Prevention

• Drug of choice: Ampicillin; Cefotaxime.
• Active Immunization: Hib Vaccine

Bordetella: General Characteristics

• Small, gram (-) coccobacilli with bipolar staining; obligate aerobes.
• Grow on Bordet-Gengou agar – pinpoint, smooth, convex, glistening, pearl-like colonies.
• Regan-Lowe agar preferred due to longer shelf life; produces grayish-white colonies.

Bordetella Species

• Bordetella pertussis: Cause Pertussis or Whooping cough.
• Bordetella parapertussis: Cause similar disease.
• Bordetella bronchiseptica: Causes disease in animals, occasionally in humans.

Bordetella pertussis: Antigenic Structure and Virulence Factors

• Filamentous hemagglutinin and fimbriae mediate ciliated cell adhesion.
• Pertussis toxin causes systemic effects.
• Adenylate cyclase inhibits phagocytic function.

Pertussis or Whooping Cough

• Communicable disease transmitted via infected droplets.
• Systemic manifestations related to pertussis toxins.

Pertussis or Whooping Cough: Clinical Manifestations

• Incubation period is 5-21 days followed by catarrhal, paroxysmal, and convalescent stages.
• Catarrhal stage: Mild coughing and sneezing with high infectivity.
• Paroxysmal stage: Coughing fits with a whoop, vomiting, cyanosis, and convulsions.
• Convalescent stage: Slow recovery.

Pertussis or Whooping Cough: Laboratory Diagnosis and Treatment

• Leukocytosis of 16,000-30,000 cells/mm3 with lymphocytosis.
• Diagnosis: Culture via nasopharyngeal swab on Bordet-Gengou, Regan-Lowe agar, Antigen detection by FA, PCR.
• Treatment: Erythromycin.
• Active immunization: DPT vaccine.

Legionella pneumophila

• Rod-shaped but difficult to stain, faintly gram-negative.
• Motile when freshly isolated visualized with Dieterle's silver impregnation and fluorescent antibody method

Legionella pneumophila: Natural Habitats and Transmission

• Found in lakes, streams, rivers, thermally heated water, and soil.
• Transmitted via airborne exposure from contaminated water
• Most cases are male, over 50, with risk factors like smoking, chronic pulmonary disease, high alcohol consumption, and immunocompromised status.

Legionnaire's Disease: Clinical Manifestations

• Incubation period of 2-10 days.
• Causes pneumonia, ranging from mild to adult respiratory distress syndrome.
• Abrupt high fever, cough, chills, headache, myalgia, and confusion.

Legionnaire's Disease: Laboratory Diagnosis and Treatment

• Diagnosis: Specimens like bronchial washings, pleural fluid, lung biopsy, blood; direct smears like DFAT, silver stain; culture on BCYE agar; serologic tests for antibody titer.
• Treatment: Macrolides, Quinolones, Doxycycline.
• Control: Hyperchlorination and superheating of water systems, beta-lactams and aminoglycosides are ineffective.

Mycoplasma pneumoniae

• Smallest bacteria lacking a rigid cell wall, resistant to penicillin but inhibited by tetracycline/erythromycin; can grow in cell-free media.
• Primary atypical pneumonia cause: In people between 5-20 years of age, a fever, headache, sore throat, and dry cough.

Mycoplasma pneumoniae: Laboratory Diagnosis and Treatment

• Gram stain not performed; small round "fried egg" colonies.
• Cold agglutinins on human erythrocytes.
• Tetracycline/Macrolides are Drugs for treatment

Chlamydiae: General Characteristics and Morphology

• Obligate intracellular parasites with tropism for columnar epithelial cells lining mucous membranes.
• Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae (TWAR agent).
• Elementary body (EB), small, dense spherical body, 0.2-0.4u, Infectious form
• Reticulate body (RB), larger in size, 0.6-1.0 u, intracellular, multiply by binary fission, Organisms stain purple with Giemsa

Chlamydiae: Inclusions, Cell Cultures, Treatment, Diagnostic

• C. trachomatis Inclusions: Compact and stain brown with iodine
• C. psittaci and C. pneumoniae inclusions do not stain brown with iodine
• McCoy cells, Embryonated egg
• Diagnostic Serologic tests: microlF for specific IgM
• Treatment Tetracycline and Sulfonamides

Chlamydiae

• C. trachomatis: Round, vacuolar Inclusions, Glycogen, YES,EB Round,Yes sulfonamides, 15 Servovars Mode of Transmision Person to person, vertical causing Trachoma, Infant pneumonia, lymphogranuloma venereum
• C. pneumoniae: Round, dense Inclusions, No Glycogen, Pear shaped, No sulfonamides, 4 Servovars, Airborn Transmision, causing Pneumonia, bronchitis, pharyngitis, sinusitis
• C. psittaci: Large variable Inclusions, No Glycogen, Round, No sulfonamides, Round Servovars, Airborne-bird screata Trasmission, causing Psittacosis, Pneumonia, Fever, of unexplained origin

Corynebacterium, Actinomycetes, Nocardia

• Actinomyces israelii Gram (+) may form chains or filsments, causes lumpy jaw, shows lesions due Sulfur Granules
• Nocardia asteroides - Gram (+) nonsporeforming, produces filaments, Partially acid-fast and causes diseases in Immunocompromised host leads to pulmonary infections

Nocardia vs. Actinomyces

• Distinguishable by Oxygen requirements, acid fast stainingm habitat, diseases and treatment.
• Nocardia aerboic, weakly acid fast, Soil, causes Pulmonary Infectios in immunocompromised individuals. Treatments: Sulfonamides
• Actinomyces anaerobic , does not stain , oral Cavitiy tracts, oral absces. Trreatments Penicillin
• Mnemonic for treatment: "SNAP" Sulfonamides → Nocardia, Actinomyces Penicillin

Corynebacterium diphtheriae

• Gram (+), nonsporeforming, nonmotile bacilli, Chinese character Microscopic appearance, Beaded with metachromatic Granules, produces exotoxin. Diphtheria, Greyish-black membrane like structure in the throat, Rarely or do produce Bacterimeia

Corynebacterium diphtheriae: Laboratory Diagnosis and Treatment

• Gram stain : "chinese character" with metachromatic granules
• Culture on Loeffler's medium and K tellurite blood agar. Diphtheria antitoxin and Penicillin treat

Corynebacterium diphtheriae: Prevention

• DPT Immunization
• Uniform morphology with 3 colony types: gravis, intermedius, mitis