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1 Respiratory Infections
Chapter 21:
Diseases of the Respiratory System
2 Components of the Respiratory System
• mucus-secreting epithelium cells in upper tract traps microbes
• cilia, expectorating helps expel trapped microbes
A. Upper respiratory tract (URT):
– nasal cavity
– pharynx
– larynx
– trachea
– bronchi
B. Lower respiratory tract:
– Lungs
– Bronchioles
– Alveoli (gas exchange, macrophages present)
3 Lower Respiratory Tract: Bronchioles terminate in alveoli
• no normal flora below larynx
• Organisms inhibit gas exchange
• macrophages in alveoli engulf particles and microbes
4 Diseases of the Upper Respiratory Tract
Acquired through the inhalation of droplet nuclei from infected persons
1. Pharyngitis (sore throat): an infection of the pharynx and can be caused by several bacteria or viruses
2. Diphtheria
3. Common cold- viral
4. Ear infections
5 Bacterial URT Disease: Streptococcal Pharyngitis
• Causative agent: Streptococcus pyogenes
• Less than 10% of pharyngitis
• gram + streptococcus
• known as “strep throat” is most common in children 5-15 years old
• Transmission:
• Acquired by inhaling droplet nuclei from active cases or healthy carriers
• family pets can also be carriers
6 Bacterial URT Disease: Streptococcal Pharyngitis
• Signs and Symptoms:
• tender tonsils with white pus-filled lesions, high fever, acute throat soreness, chills, headache
• pyogenic and pyrogenic
• Prevention and treatment
• rapidly diagnosed with ELISA test (Ch. 18)
• antibiotics given because of sequelae
• rheumatic fever
• glomerulonephritis
• scarlet fever if S. pyogenes strain is toxigenic (Ch. 19)
7 Streptococcal Pharyngitis Sequelae: Rheumatic Fever pg. 720
• Sequelae of approximately 3% of non treated streptococcal infections
• can result in permanent damage to the mitral heart valve.
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• appears approx. 20 days after of the initial streptococcal infection (strep throat, scarlet fever)
• Treatment:
• anti-inflammatory drugs
• life-long antibiotic prophylaxis is recommended following a single case.
• prophylactic antibiotics to prevent bacterial endocarditis prior to dental visits, piercing, etc.
8 Streptococcal Pharyngitis Sequelae: Rheumatic Fever pg. 720
Signs and Symptoms:
• fever
• chorea (incoordination)
• malaise
• Arthritis
• 2-5% mortality
• immune complexes damage the heart valve in a “cross-reaction”
• Cause mitral valve deformity
• Contribute to bacterial colonization
9 Streptococcal Pharyngitis Sequelae: Glomerulonephritis pg. 612
• Immune complex disease causes inflammation and damage to the glomeruli of the kidneys
• strains of S. pyogenes contain antigens in their cell walls that resemble tissue present in glomerular tissue
• immune system antibiodies bind with kidney tissue (cross-reaction)
• initiates inflammatory response, attracts macrophages
• causes proteins and blood to leak into urine
10 Bacterial URT Disease: Diphtheria
1 • Although fewer than 5 cases per year in the U.S., this disease was once a feared killer
• 100 years ago, 30-50% infections were fatal
• Sequelae include: myocarditis, polyneuritis and neurological problems
2 • Causative agent: Corynebacterium diphtheriae containing a prophage that produces an exotoxin
• gram + rod, palisade arrangement (cells appear to snap in half)
11 Bacterial URT Disease: Diphtheria
• 3 strains gravis, intermedius and mitis
• C. diphtheriae gravis is the most severe
• Toxin consists of 2 proteins
• fragment A inhibits protein synthesis, leading to cell death
• fragment B target mammalian heart and nervous system cells
• one molecule of toxin can kill a cell!
• “curing” the bacterium of the bacteriophage eliminates the ability to produce toxin
12 Bacterial URT Disease: Diphtheria
1 • Transmission:
• humans are only known reservoirs of C. diptheriae
• may be carriers
• spread by droplets of respiratory secretions
• colonizes the pharynx (other non-toxigenic strains can infect skin, conjunctiva, mucous membranes)
• early symptoms similar to common cold
2 • Pseudomembrane within 2-3 days forms over tonsils, palate
• made of clotted blood, microbes, WBC and damage cells can block air passageway
• membrane will reform if removed, but removal is necessary to open airway
13 Bacterial URT Disease: Diphtheria
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• Treatment
• antibiotics: erythromycin, penicillin (no effect on toxin)
• antibiotics immediately stop shedding
• Chronic carriers may shed for 6 months
• anti-toxin antibodies: to counteract the toxin
• Antitoxin made in horses (candidate for recombinant technology?)
• Serum sickness a possibility?
• Only effective against unbound toxin
• Vaccine: DTaP (diphtheria, tetanus, pertussis)
• Even with treatment, 5-10% mortality rate (higher in susceptible groups)
14 Bacterial URT Disease: Diphtheria
Diphtheria is not controlled in other parts of the world
• U.S. must continue vaccinations to prevent epidemics
• keeps U.S. herd immunity at high levels
15 Viral URT Disease: The Common Cold (Coryza)
• not life-threatening
• Causative agent(s):
• Rhinoviruses –responsible for 50% of cases
• Coronaviruses are the second most common cause of colds
• Ubiquitous and present year round, but most infections occur in early fall or spring
• about 200 viruses cause the common cold
• Vaccine against common cold nearly impossible
16 Viral URT Disease: The Common Cold (Coryza)
• Transmission:
• Most likely spread by fomites rather than contact
• Surfaces contaminated mucous secretions
• Portal of entry by the mucous membranes of nose, eyes, respiratory tract
• Signs and Symptoms:
• 2-4 day incubation period and lasts about 1 week
• excessive mucus secretion, sneezing, inflammation of mucous membranes, sore throat, headache, cough
17 Viral URT Disease: The Common Cold (Coryza)
• Prevention and Treatment:
• Self limiting
• Antibiotics are ineffective
• Hand washing and keeping hands away from the face
• Even cold water destroys rhinoviruses
• OTC remedies to alleviate symptoms
18 Bacterial URT Disease: Ear Infections
1 • Commonly occur as otitis media in the middle ear and otitis externa
2 • Seventy-five percent of children experience at least one episode of otitis media by their third birthday
19 Bacterial URT Disease: Ear Infections
• Causative agent(s):
• Otitis media: Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae and
several viruses
• Otitis externa: Staphylococcus aureus, Pseudomonas aeruginosa (swimmer’s ear)
• Transmission:
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• In otitis media, phayngeal organisms pass into the Eustachian tube and cause infection
• As children age, eustachian tube grows and angle changes
• Accounts for the lack of ear infections in adults
20 Bacterial URT Disease: Ear Infections
Treating middle ear infections
• Prevention and Treatment:
• antibiotics (penicillin, amoxicillin)
• sterile fluid may remain in the ear
• tubes in the ears allow for drainage and to prevent recurrent infections.
• removal of adenoids
21 Infections of the Lower Respiratory Tract
• Whooping cough
• Classic pneumonia
• Mycoplasma pneumonia
• Legionnaire’s Disease
• Tuberculosis
• Q fever
• Anthrax
• SARS
• Pneumocystis pneumonia
22 Bacterial LRT Infection: Whooping Cough
• Causative agent: Bordatella pertussis
• small, aerobic, gram-negative coccobacillus with capsule
• produces:
• hemagglutinin: antigens that help Bordatella to attach to cilia
• Pertussis Exotoxin- paralyzes cilia on respiratory cells and cause inflammation of respiratory tract
• Endotoxin- LPS
• Bordatella bronchiseptica (normal flora of canine respiratory tract causes “kennel cough”)
23 Bacterial LRT Infection: Whooping Cough
• Transmission
• Uncommon in U.S. because of vaccination, but causes an estimated 300,000 deaths a year worldwide
• highly contagious disease known only in humans
• Contact with respiratory droplets
• Inflammation of trachea + mucus production and lack of cilia movement may plug airways→coughing
spasms
24 Bacterial LRT Infection: Whooping Cough
• The disease progress through three stages:
• 1. Catarrhal: characterized by fever, sneezing, vomiting, and mild, dry persistent cough
• 2. Paroxysmal: mucus and masses of bacteria fill the airway
• strong violent cough interrupted by “whoops” is classic (only found in 50% of patients)
• cyanosis may occur due to decreased oxygen in blood
• keeping airway open difficult and account for high death rate in patients <1 y
25 Bacterial LRT Infection: Whooping Cough
1 • 3. Convalescent: enter this stage after 1-6 weeks.
• Secondary infections are common at this stage
• mild coughing can last for months
2 • Diagnosis:
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• Culture of organism is gold standard (may take 2 weeks)
• Swab of nasopharynx with calcium alginate (not cotton swab)
• Organism is fastidious
26 Bacterial LRT Infection: Whooping Cough:
The annual incidence of whooping cough in the U.S and incidence by age group
27 Bacterial LRT Infection: Whooping Cough
• Treatment and Prevention:
• Antibiotics are somewhat helpful
• supportive measures (suctioning, oxygen, nutrition)
• DTP vaccine had some reactions (5-20 deaths/year)
• Contained formalin inactivated B. pertussis cells
• DTaP vaccine (acellular vaccine-subunit vaccine)
• 5 doses: 2, 4 , 6 months, 15-18 months, and the fifth dose at ages 4-6 years
• Tdap, Td vaccines (adolescent and adult formulation)
28 Bacterial LRT Infection:
Classic Pneumonia
• An inflammation of lung tissue, can be caused by various microorganisms/parasites/ chemicals/ radiation/
allergies
• #1 infectious disease killer in US
• Organisms colonize upper respiratory tract and then accidentally enter the lower respiratory tract
• Pneumonias classified as either bronchial or lobar
• May involve pleurisy: inflammation of the membranes surrounding lungs
29 Bacterial LRT Infection:
Classic Pneumonia
Several bacteria cause pneumonia
• Streptococcus pneumoniae*
• causes Pneumococcal pneumonia
• Smooth capsulated strains are major virulence factor
• Staphylococcus aureus*
• Klebsiella pneumoniae**
• Haemophilus influenzae**
• Pseudomonas aeruginosa **
*gram positive cocci
**gram negative bacilli
30 Bacterial LRT Infection:
Classic Pneumonia
• Transmission
• Commonly carried as normal flora
• Heavy load (high dose) of organisms are inhaled into lungs
• May be endogenous or direct contact of respiratory secretions from a carrier
• 2nd most common nosocomial infection
• Signs and Symptoms:
• Presence of organisms elicit inflammatory response, fluid accumulation
• cough, fever, chest pain, shortness of breath, rapid heart rate, rapid breathing, and production of sputum
with cough
31 Bacterial LRT Infection:
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Classic Pneumonia
• Treatment:
• Antibiotics: penicillin
• Onset of resistant strains requires other antibiotics
• immunity only lasts a few months after infection
• Prevention: Vaccines
• Pneumovax: contains 23 of the 85 strains of S. pneumoniae
• 23 strains cause 88% of pneumonias
• recommended for >65 yr and <2 yrs
• 3 HiB (Haemophilus influenzae B) vaccines
• Prevnar: Streptococcus pneumoniae vaccine
• not for person >5 years
32 Bacterial LRT Infection: Mycoplasmal Pneumonia
• Causative agent: Mycoplasma pneumoniae
• Lack peptidoglycan cell wall: no cell morphology or gram reaction
• Bacterial cell adhere to respiratory cells and cause ciliated cells to slough off
• Primary atypical pneumonia or Walking pneumonia:
• URT infection with fever, cough, headache and malaise
• 3-10% contract a mild pneumonia
• patients often remain ambulatory, unlike classic pneumonia cases
33 Bacterial LRT Infection: Mycoplasmal Pneumonia
• Transmission:
• respiratory droplets
• 12-14 day incubation
• Diagnosis: isolation of M. pneumoniae (2-3 week growth rate)
• Prevention and Treatment:
• Azithromycin, erythromycin, fluroquinolones
• Why won’t penicillin work?
• No vaccine available, mild non-lethal disease
34 Bacterial LRT Infection: Legionnaires’ Disease
• New genus named in 1976 many war veterans attending a convention became victims of this mysterious
ailment
• 29 died
• antibiotics would have been effective
• Causative agent: Legionella pneumophila:
• weakly gram-negative, strictly aerobic bacillus
• fastidious nutritional requirements
• most Legionella species are found in soil or water
35 Bacterial LRT Infection: Legionnaires’ Disease
2 • Transmission:
• Inhalation of mist or water vapor contaminated with Legionella
• Not transmitted person to person
• Air conditioners, ornamental fountains and produce sprayers have been implicated in spread of disease
• Smokers or people with impaired lung function are more susceptible
36 Bacterial LRT Infection: Legionnaires’ Disease
• Signs and Symptoms:
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• Organisms colonize near the alveoli in the lungs
• survives within the macrophage; prevents fusion of phagosome and lysosome so
• Symptoms similar to classic pneumonia 2-14 days after exposure
• fever headache, fluid in lungs, chest and abdomen pain
• LPS shock, sweating and mental disorders rare
• Prevention and Treatment:
• regular disinfection of water features, use of chlorine in potable water sources
• erythromycin and penicillin
37 Bacterial LRT Infection: Tuberculosis (TB)
• a.k.a. consumption
• been found in Egyptian mummies ca. 2400 B.C
• usually a respiratory infection, but can attack any part of the body
• remains a massive global health problem (1/3 of world’s population has TB)
• Infecting 10 million new cases, and killing 3 million annually makes TB the biggest bacterial killer in the
world.
• appearance of resistant strains (MDR-TB, XDR-TB)
• Atypical mycobacteria, such as Mycobacterium avium-intracellulare complex (MAC) cause TB in AIDS
patients
38 Bacterial LRT Infection: Tuberculosis (TB)
• Causative agent: Mycobacterium tuberculosis
• Straight or slightly curved rods, extremely slow-growing
• Acid fast bacilli contain mycolic acids; stain used for preliminary diagnosis because of the slow culture
time in lab
• highly resistant to drying
• obligate aerobes: grow well in upper portions of lungs
39 Bacterial LRT Infection: Tuberculosis (TB)
• Transmission:
• acquired by inhalation of respiratory secretions containing the Mycobacterium bacilli
• Minimum infectious dose = 10 organisms
• phagocytized by alveolar macrophages, but grow within the macrophage
• Grow, replicate, lyse macrophage and infect new cells
• Can infect lungs, kidneys, bones, brain during secondary or reactivation TB
40 Bacterial LRT Infection: Tuberculosis (TB)
• Manifestations: 3 outcomes of infection
• 1. Active TB: neutrophil infiltration and fluid accumulation in alveoli→ produces pneumonia-like symptoms
• reproduction in macrophages, rupture and release of microbes
• inflammatory reaction
• Tubercle formation
• immune system walls off organisms = tubercles in lung (can see them on chest X-ray)
• due to cell mediated immune response
• contain live organisms and macrophages, walled off by fibroblasts, lymphocytes and neutrophils
• Tubercles may become calcified
41 Bacterial LRT Infection: Tuberculosis (TB
2 • 2. Latent TB infection (most persons exposed to TB):
• have no symptoms
• can't spread TB to others
• usually have a positive skin test reaction/normal x-ray
• can develop active TB disease if they do not receive treatment for latent TB infection
• 3. Reactivation TB: occurs when bacilli are released from tubercle due to immunosuppression
• a bad cough that lasts 3 weeks or longer
• pain in the chest
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• coughing up blood or sputum
• Infectious to others
42 Bacterial LRT Infection: Tuberculosis
43 Bacterial LRT Infection: Tuberculosis
44 Bacterial LRT Infection: Tuberculosis (TB)
• Diagnosis
• cultures must be kept for 8 weeks to call negative test
• PCR which amplify a specific target gene are promising developments
• screening by PPD (purified protein derivative)
• hypersensitivity to PPD means exposure, but not active case of TB
• Prevention and Treatment:
• vaccine: BCG (not approved in the US)
• Combined antibiotic therapy to ↓chance of resistance, 6-24 months
• Resistant strains worldwide
• http://www.ted.com/index.php/talks/james_nachtwey_fights_xdrtb.html
45 Bacterial LRT Infection: Anthrax
Pg. 691-2
• Causative agent:
• Bacillus anthracis
• Gram Positive, endospore-forming rod, facultatively anaerobic
• Multiple Disease Manifestations:
• 1. Cutaneous anthrax: endospores enter cuts in skin
• 2. Respiratory anthrax: almost always fatal regardless of treatment
• occupational exposure on farms or industries that handle wool hides
• 3. Intestinal anthrax
46 Bacterial LRT Infection: Anthrax
• Transmission:
• Inhalation of endospores→Spores germinate in alveoli
• Organisms are phagocytized, but are not killed by macrophages
• No person to person transmission
• Exotoxins produce cardiovascular shock, septicemia within hours of infection, death 2-3 days
• Prevention and Treatment:
• Antibiotics for long periods of time if exposure is suspected (may take up to 60 days for all spores to
germinate)
• Ciprofloxacin, penicillin, erythromycin
• Animal immunization to protect farmers
47 Viral LRT Infection: Severe Acute Respiratory Syndrome (SARS)
• Nov. 2002: people in China began falling sick of a new respiratory disease
• by epidemic end in July 2003, it had been diagnosed in 8,098 people, killed 774 and spread to 29
countries
• Causative agent:
• a previously unknown coronavirus (SARS-CoV)
• common cold type virus, not influenza type virus
• Symptoms: high fever, dry cough, shortness of breath, difficulty breathing, and X-rays indicating pneumonia
48 Viral LRT Infection: Severe Acute Respiratory Syndrome (SARS)
• Transmission:
• Virus spread by close contact with an infected person, usually by exhaled or coughed aerosol droplets
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• Touching contaminated objects
• Prevention and Treatment:
• Supportive care
• Is SARS gone?
• reservoirs?
• emerging virus?
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