Respiratory Infections Components of the Respiratory System

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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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