Chapter 22 - Microbial Diseases of the Respiratory System

Upper respiratory system

Nose, pharynx, middle ear, and eustachian tubes

Saliva and tears protect mucosal surfaces

Lower respiratory system

Larynx, trachea, bronchial tubes, and alveoli

Ciliary escalator and alveolar macrophages provide protection; respiratory mucus protects mucosal surfaces

Ciliary escalator

ciliated mucosal cells of the lower respiratory tract that move inhaled particulates away from the lungs

Normal microbiota of the respiratory system

Suppress pathogens by competitive inhibition in upper respiratory system

Lower respiratory system is sterile

Pharyngitis

Inflammation of the pharynx; sore throat

Laryngitis

Inflammation of the larynx, or voice box

Tonsillitis

Inflammation of the tonsils

Sinusitis

Infection/inflammation of the nasal sinuses; usually self-limiting

Epiglottitis

A disease in which the epiglottis becomes inflamed and enlarged and may cause an upper airway obstruction; caused by Haemophilus influenzae

Streptococcal Pharyngitis (Strep Throat)

S. pyogenes infection of the tonsils and pharynx causing local inflammation, fever, tonsillitis, sore throat and frequently swollen lymph nodes; diagnosed by rapid antigen test

Streptococcus pyogenes (Group A)

Causes strep throat; resistant to phagocytosis; streptokinases lyse clots and streptolysins are cytotoxic;

Scarlet fever

Caused by erythrogenic toxin produced by lysogenized S. pyogenes; fever and a red rash

Diphtheria

Caused by Corynebacterium diphtheriae (gram-positive pleomorphic rod) via an exotoxin encoded by a prophage. Potent exotoxin circulates in blood and can damage heart and kidneys; Forms tough gray membrane in throat composed of fibrin and dead tissue that can block air passageway; prevented by DTaP vaccine which contains a diphtheria toxoid

Cutaneous diphtheria

Infected skin wound leads to slow healing ulcer; adults over 30

Otitis media

Infection of the middle ear common in childhood; pus puts pressure on eardrum; can cause conductive hearing loss; caused by S. pneumoniae, nonencapsulated H. influenzae, M. catarrhalis, S. pyogenes, and RSV; treated with broad-spectrum penicillin

Common cold

Caused by over 200 different viruses including rhinoviruses (most common), coronaviruses, and enterovirus D68 (least common); sneezing, nasal secretion, congestion (no fever); secondary laryngitis and otitis media; treatment to relieve symptoms (cough suppressants and antihistamines)

Rhinoviruses

Number one cause of common cold; thrive in temperatures lower than body temperature; transmitted via aerosols and direct contact

Pertussis (whooping cough)

Caused by Bordetella pertussis (gram-negative coccobacillus); airborne, very contagious; capsule allows attachment to ciliated cells in respiratory tract and shuts down ciliary escalator; prevented by DTaP vaccine; treated with macrolides eg erythromycin

Pertussis stages

Catarrhal Stage: upper respiratory infection similar to common cold

Paroxysmal Stage: whooping cough (mainly at night); gasping for air; flushed or cyanotic cheeks

Convalescent Stage: cough decreases, strength returns; may take months

Tuberculosis

Airborne transmission; most commonly caused by Mycobacterium tuberculosis; M. bovis (bovine tuberculosis) <1% of cases; M. avium-intracellulare complex common in late stage AIDS patients

Mycobacterium

Acid-fast bacillus; obligate aerobe; 20-hr generation time; lipids in wall help it resist drying and antimicrobial drugs

Tuberculosis pathogenesis

Colonization of alveoli causes inflammatory response; macrophages ingest bacterium, survives ingestion (protected by high lipid content of cell wall)

Tubercle forms (walled off bacteria surrounded by macrophages); tubercles heal and become calcified forming Ghon's complexes that can allow the bacteria to be latent, sometimes for years; Tubercle can break down and release bacteria into cardiovascular and lymphatic systems resulting in miliary (disseminated) tuberculosis

Diagnosis of Tuberculosis

Tuberculin skin test screening

Positive reaction means current or previous infection

Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria

Rapid blood test for IFN-gamma and NAAT provides higher specificity and less cross-reaction

NAAT

Nucleic acid amplification test

Treatment of Tuberculosis

Minimum of 6 months of drug therapy due to slow growth and dormancy

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

Second-line drugs: aminoglycosides, fluoroquinolones, para-aminoslicyclic acid (PAS)

Multi-drug-resistant (MDR) strains: resistant to first-line drugs

Extensively drug-resistant (XDR) strains: resistant to second-line drugs

BCG vaccine

Live culture of avirulent M. bovis

Bacterial pneumonia

often caused by Streptococcus pneumoniae; is the only form of pneumonia that can be prevented through vaccination

Atypical pneumonia

Pneumonia caused by microbes other than S. pneumoniae

Lobar pneumonia

Pneumonia that affects larger areas of the lungs, often including one or more sections, or lobes, of a lung

Bronchopneumonia

acute inflammation of the walls of smaller bronchioles with spread to alveoli

Pleurisy

Painful inflammation of the pleura

Pneumococcal pneumonia

-Caused by S. pneumoniae (Gram-positive; encapsulated diplococci; 90 serotypes)

-Infected alveoli of the lung fill with fluids and RBCs; interferes with oxygen uptake

-Diagnosis: optochin-inhibition test, bile solubility test, or antigen in urine

-Treated with macrolides and fluoroquinolones

-Prevented with conjugated pneumococcal vaccine

Haemophilus influenzae pneumonia

Symptoms similar to those of pneumococcal pneumonia; children under 5 and adults over 65 are most at risk; prevented by HIB vaccine (reduces incidence in children by 99%); diagnosis by culture on media containing X and V factors; treated with cephalosporins

Mycoplasmal pneumonia

Primary atypical pneumonia or walking pneumonia caused by Mycoplasma pneumoniae that has a "fried-egg" appearance microscopically

Mild but persistent respiratory symptoms; low fever, cough, headache (Common in children and young adults)

-Diagnosis: PCR and serological testing

-Treated with tetracyclines

Legionellosis

Legionnaires' disease; caused by Legionella pneumophila - aerobic gram-negative bacillus that thrives in water and air conditioning units; another type of bacterial pneumonia; transmitted by inhaling aerosols; high fever and cough (similar to Pontiac fever); treated with azithromycin and macrolides

Psittacosis (Ornithosis)

Caused by Chlamydophila psittaci

Gram-negative intracellular bacterium

Transmitted to humans by elementary bodies from bird droppings transmitted through air

Fever, headache, chills, disorientation

Diagnosis: growth of bacteria in eggs or cell culture

Treated with tetracyclines

Chlamydial pneumonia

- caused by Chlamydophila pneumoniae

- transmitted person to person

- mild respiratory illness common in young people; resembles mycoplasmal pneumonia

- possible association with artherosclerosis

- diagnosis: serological tests

- treated with tetracyclines

Q fever

Caused by Coxiella burnetii (obligate intracellular gram-negative gammaproteobacteria) that is transmitted to farm animals from ticks and to humans from inhalation of aerosols from animals and unpasteurized milk; treated with doxycycline and chloroquine for chronic infections

Acute Q fever

High fever, muscle aches, headache, coughing

Chronic Q fever

Endocarditis (may occur years after infection); can be fatal

Melioidosis

Caused by Burkholderia pseudomallei (Gram-negative rod)

Endemic in moist soils of southeast Asia and northern Australia

Mainly affects the immunocompromised

Symptoms include pneumonia or tissue abscesses and severe sepsis

Transmission is by inhalation, puncture wounds, and ingestion

Treated with ceftazidime

Respiratory Syncytial Virus (RSV)

- Most common viral respiratory disease in infants

- Almost all children are infected by age 2

- 14,000 deaths annually

- Causes cell fusion (syncytium) in cell culture

- Coughing and wheezing for more than a week

- Diagnosis: serological test for viruses and antibodies

- Treated with ribavirin and palivizumab

Viral pneumonia

A complication of influenza, measles, or chickenpox

Viral etiology suspected if no cause determined since few labs can test directly for these viruses

SARS (severe acute respiratory syndrome)

Potentially life-threatening viral infection that usually starts with flulike symptoms.

SARS-associated coronavirus (SARS-CoV)

Viral pneumonia causing SARS that emerged in Asia in 2003

Middle East Respiratory Syndrome (MERS)

Caused by Middle East respiratory syndrome coronavirus (MERS-CoV)

Similar to SARS

100 deaths in the Middle East from 2012 to 2014

COVID-19

Caused by SARS-CoV-2 (enveloped + RNA virus); spike protein attaches to ACE-2 receptors (on many organs including lungs, heart, kidneys, GI tract); makes 8 proteins that block interferon; transmitted via fomites and droplets; older adults, pregnant women, and those with underlying conditions most at risk; prevented with vaccine, masks and social distancing

COVID-19 symptoms

Mild/early: fever, dry cough, fatigue, loss of smell and/or taste

Other/late: shortness of breath, muscle aches, headache, chills, nausea, rash

Severe: difficulty breathing, chest pain/pressure, confusion, difficulty waking or staying awake, blue skin or lips

Critical: multiple organ involvement, blood clots

COVID-19 Treatment

Supportive care (oxygen); remdesivir (broad spectrum antiviral)

Influenzavirus

Enveloped RNA virus; contains 8 RNA segments and an outer lipid bilayer

Influenza

Chills, fever, headache, muscle aches (no GI symptoms); 3000-50000 deaths in US annually; avian, swine, and mammalian strains can mix leading to antigenic shift; HA spikes attach to host cells; NA spikes help virus bud from cell

Antigenic drift in influenza

Minor antigenic changes in HA and NA

Allow the virus to elude some host immunity

Antigenic shift in influenza

Changes great enough to evade most immunity; leads to pandemics; involves reassortment of the 8 RNA segments

Influenza treatment and prevention

Multivalent vaccine - composition determined annually based on circulating viruses; labor intensive and no long-term immunity due to antigenic variation of virus; difficult to diagnose from symptoms; treated with zanamivir (Relenza) and oseltamivir (Tamiflu) which inhibit neuraminidase

Histoplasmosis

Caused by Histoplasma capsulatum (dimorphic fungus); grows in macrophages; forms lung lesions and can rarely become severe, generalized disease; transmitted by inhalation of airborne conidia in areas with bird or bat droppings; treated with itraconazole

Coccidioidomycosis

AKA Valley fever or San Joaquin fever; Caused by Coccidioides immitis - dimorphic fungi that can cause systemic mycosis; endemic to Southwestern US, California; arthroconidia are inhaled and form spherule filled with endospores in tissues; can be asymptomatic or cause fever, coughing, and weight loss; rarely can cause symptoms resembling tuberculosis; treated with fluconazole or itraconazole

Pneumocystis pneumonia

Caused by Pneumocystis jirovecii

Asymptomatic in the immunocompetent; causes pneumonia in the immunocompromised (primary indicator of AIDS)

Found in the lining of the alveoli– Forms a cyst in the alveolar lining; Cysts rupture, releasing eight trophozoites that can spread through lungs;

Treated with trimethoprim-sulfamethoxazole

Pneumocystis jiroveci

Characteristics of both protozoa and fungi; classified as fungus based on nucleic acid and biochemical analysis

Blastomycosis

Caused by Blastomyces dermatitidis - dimorphic fungi that can cause systemic mycosis, endemic to states east of Mississippi River; symptoms similar to bacterial pneumonia; can cause cutaneous abscesses that lead to extensive tissue damage; treated with itraconazole and amphotericin B

Aspergillus fumigatus

Aspergillosis; airborne conidia can be inhaled; grows in compost

Rhizopus and Mucor

Mold spores that can be inhaled and cause respiratory disease

Stachybotrys

Black mold fungi that thrives on water damaged cellulose material. Produces a potent mycotoxin