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RESPIRATORY TRACT INFECTIONS

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Title: RESPIRATORY TRACT INFECTIONS


1
RESPIRATORY TRACT INFECTIONS
  • Department of Microbiology
  • Faculty of Medicine
  • Brawijaya University

2
The Respiratory tract
  • Most common entry point for infections
  • Pathogens that enter the respiratory system can
    infect other parts of the body
  • Upper respiratory tract
  • nose, nasal cavity, sinuses, throat and
    associated structures such as the middle ear and
    auditory tube
  • Lower respiratory tract
  • Trachea, bronchi, bronchioles, and alveoli in the
    lungs

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Protective Mechanisms
  • Normal flora Commensal organisms
  • Limited to the upper tract can include pathogenic
    microorganisms
  • Mostly Gram positive or anaerobic
  • Microbial antagonist (competition)
  • The lower respiratory system is usually sterile
    because of the action the ciliary escalator

6
Protective Mechanisms
Clearance of particles and organisms from the
respiratory tract
Cilia and microvilli move particles up to the
throat ? where they are swallowed. Alveolar
macrophages migrate and engulf particles and
bacteria in the alveoli deep in the lungs.
7
Other Protective Mechanisms
  • Nasal hair, nasal turbinates
  • Mucus
  • Involuntary responses (coughing)
  • Secretory IgA
  • Immunocompetent cells

8
Microbial Diseases of The Upper Respiratory System
  • Specific areas of the upper respiratory system
    can become infected to produce pharyngitis,
    laryngitis, tonsilitis, sinusitis and
    epiglottitis
  • These infections may be caused by several
    bacteria and viruses, often in combination

9
Bacterial Diseases of The Upper Respiratory System
  • Streptococcal Pharyngitis (Strep Throat)
  • Scarlet Fever
  • Otitis Media
  • Diphteria

10
Streptococcal Pharyngitis (Strep Throat)
  • This infection is caused by group A
    beta-hemolytic streptococci (Streptococcus
    pyogenes)
  • Gram positive cocci, katalase negative

11
Streptococcus pyogenes
  • Capsule -resistant to phagocytosis
  • Enzymes damage host cells
  • M protein adhesin

The M protein has many antigenic varieties and
thus, different strain of S.pyogenes cause
repeat infections
12
Strep Throat
  • Fever
  • Tonsillitis
  • Enlarged lymph nodes
  • Middle-ear infection
  • Treatment
  • Antibiotic ? Penicillin

13
Scarlet Fever
  • Strep throat, caused by an erythrogenic
    toxin-producing S.pyogenes, result in Scarlet
    Fever
  • S.pyogenes produces erythrogenic toxin when
    lysogenized by a phage
  • Symptoms include a red rash, high fever, and a
    red, enlarge tongue (strawberry tongue)

14
Scarlet Fever
Caused by Erythrogenic Toxin secreted by S.
pyogenes
15
Scarlet Fever
  • The erythrogenic
  • toxin is coded by a gene
  • lysogenic bacteriophage
  • within the genome of
  • S. pyogenes
  • Rash is an inflammatory reaction to the toxin

16
Infected Middle Ear(otitis media)
17
Otitis Media
  • Can occur as a complication of nose and throat
    infections
  • Pus accumulation causes pressure on the eardrum
  • Bacterial causes include Streptococcus
    pneumoniae, Haemophilus influenzae, Moraxella
    catarrhalis, Streptococcus pyogenes, and
    Staphylococcus aureus

18
Diphtheria
19
Diphtheria
  • Caused by Corynebacterium diphtheriae
  • Transmitted by droplets or fomites
  • Infects the upper respiratory tract
  • Begins with severe sore throat, low-grade fever
    and swollen lymph nodes or with skin rash, 1-6
    days after infection

20
Corynebacterium diphtheriae
  • Aerobic Gram bacillus, club-shaped morphology,
    metachromatic granules, form V and Y-shaped
    figures
  • Exotoxin inhibits protein synthesis of cells to
    which it binds, and heart, kidney, or nerve
    damage may result
  • Destroyed cells and WBC form "pseudomembrane"
    which blocks airways

21
Corynebacterium diphtheriae
  • To produce exotoxin,
  • C. diphtheriae must be infected with a
    bacteriophage carrying the toxin gene

22
An AB toxin
  • B binding subunit
  • A active subunit
  • which binds to and inhibits a eucaryotic
    ribosomal translation factor
  • Vaccine is diphtheria toxoid

23
Diphtheria
24
Diphtheria
  • Laboratory diagnosis isolation of the bacteria
    and the appearance of growth on differential
    media, ELEK test, PCR for detection tox gene
  • Antitoxin must be administered to neutralize the
    toxin, and antibiotics can stop growth of
    bacteria
  • Routine immunization ? diphtheria toxoid in the
    DTaP vaccine
  • Slow healing skin ulcerations are characteristic
    of cutaneous diphtheria

25
Viral Diseases of The Upper Respiratory System
  • THE COMMON COLD
  • Any one of approximately 200 different viruses
    can cause the common cold Rhinoviruses cause
    about 50 of all, Coronaviruses 15 20 . In
    about 40 of cases no causative agent can be
    identified
  • Symptoms include sneezing, nasal secretions, and
    congestion
  • Sinus infections, lower respiratory tract
    infections, laryngitis, and otitis media can
    occur as complication

26
  • THE COMMON COLD
  • Colds are most often transmitted by indirect
    contact
  • Rhinovirus grow best slightly below body
    temperature
  • The incidence of colds increases during cold
    weather, possibly because increased interpersonal
    indoor contact or physiological changes
  • Antibodies are produced against the specific
    viruses

27
Microbial Diseases of The Lower Respiratory Tract
  • Many of the same microorganisms that infect the
    upper respiratory system also infect the lower
    respiratory system
  • Diseases of the lower respiratory include
    bronchitis and pneumonia
  • Bacterial, viral and fungal infection can cause
    Inflammation of the lung with fluid filled alveoli

28
Bacterial Diseases of The Lower Respiratory System
  • Bacterial Pneumonias
  • Pertussis (Whooping Cough)
  • Tuberculosis ? (module)
  • Melioidosis

29
Bacterial Pneumonias
  • Typical Pneumonia is caused by Streptococcus
    pneumoniae
  • ( Diplococcus pneumoniae Pneumococcus)
  • Atypical Pneumonias are caused by other
    microorganisms

30
Pneumococcal Pneumonia
31
Pneumococcal Pneumonia
  • Is caused by encapsulated S.pneumoniae
  • The bacteria can be identified by the production
    of alpha hemolysin, inhibition by optochin, bile
    solubility, and through serological test
  • Symptoms are fever, breathing difficulty, chest
    pain, and rust-colored sputum
  • Treatment penicillin, fluoroquinolones
  • Prevention pneumococcal vaccine consist of 23
    serotypes of S.pneumoniae

32
Haemophilus influenzae Pneumonia
  • H.influenzae is a gram-negative coccobacil
  • Alcoholism, poor nutrition, cancer, and diabetes
    are predisposing factors for H.influenzae
  • Treatment 2nd generation of cephalosporins that
    are resistant to beta-lactamases produced by many
    H.influenzastrains

33
Mycoplasmal Pneumonia
  • Mycoplasma pneumoniae causes mycoplasmal
    pneumonia it is an endemic disease
  • The mycoplasmas, which do not have cell walls, do
    not grow under the condition normally used to
    recover most bacterial pathogens

34
  • M.pneumoniae produces small fried egg colonies
    after two weeks incubation on enriched media
    containing horse serum and yeast extract
  • Diagnosis is by PCR or serological test
  • Treatment tetracycline

35
Legionellosis
  • This disease is caused by aerobic gram-negative
    rod Legionella pneumophila
  • The bacterium can grow in water, such as
    air-conditioning cooling towers, and then
    disseminated in the air
  • This pneumonia does not appear to be transmitted
    from person to person
  • Bacterial culture, FA test, and DNA probes are
    used for laboratory diagnosis
  • Treatment Erythromycin

36
Psittacosis (Ornithosis)
  • The term psittacosis is applied to the human
    Chlamydia psittaci disease acquired from contact
    with birds and also the infection of psittacin
    birds (parrots,parakeets,etc)
  • Elementary bodies allow the bacteria to survive
    outside a host
  • Commercial bird handlers are most susceptible to
    this disease
  • The bacteria are isolated in embryonated eggs,
    mice, or cell culture. Identification is based on
    FA staining
  • Treatment tetracyclines

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Chlamydial Pneumonia
  • Chlamydia pneumoniae, causes pneumonia it is
    transmitted from person to person
  • C.pneumoniae produces round,dense,
    glycogen-negative inclusion that are
    sulfonamide-resistant
  • The elementary bodies some time have a
    pear-shaped appearance
  • Suggesting that C.pneumoniae associated with
    atherosclerotic coronary artery and cvd
  • Tetracycline is used for treatment

39
Chlamydia pneumoniae
40
Q Fever
  • Obligately parasitic, intracellular Coxiella
    burnetii causes Q Fever
  • The disease is usually transmitted to humans
    through unpasteurized milk or inhalation of
    aerosols in dairy barns
  • Mild respiratory disease lasting 1 2 weeks
    occasional complication such as endocarditis
    occur
  • Treatment doxycycline and chloroquin

41
Melioidosis
  • Melioidosis is caused by Burkholderia
    pseudomallei, a gram-negative rod formerly placed
    in the genus of Pseudomonas
  • Melioidosis is transmitted by inhalation,
    ingestion, or through puncture wounds
  • Symptoms include pneumonia, sepsis, and
    encephalitis
  • Most common in Southeast Asia and northern
    Australia
  • Treatment Ceftazidime

42
Pertussis (Whooping Cough)
  • Pertussis is caused by Bordetella pertussis
  • B.pertussis is a small, obligately aerobic
    gram-negative coccobacillus
  • The virulent strain posses a capsule
  • The bacteria attach specifically to ciliated
    cells in the trachea, first impeding their
    ciliary action and then progressively destroying
    the cells
  • The filamentous hemagglutinin mediates adhesion
    to ciliated epithelial cells

43
Pertussis (Whooping Cough)
  • B.pertussis produce several toxins. The tracheal
    toxin ?damage to the ciliated cells, pertussis
    toxin ? blood stream and associated with systemic
    symptoms of the disease
  • The initial stage of pertussis resemble a cold
    and is called catarrhal stage
  • The paroxismal (second) stage ? deep cough
  • The convalescence stage can last for months
  • Regular immunization ? decreases the incidence of
    pertussis (DTaP)
  • Treatment erythromycin

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Viral diseases of The Lower Respiratory System
  • VIRAL PNEUMONIA
  • Viral pneumonia can occur as a complication of
    influenza, measles, or even chickenpox
  • The etiologies are not usually identified in a
    clinical laboratory because of the difficulty in
    isolating an identifying viruses

46
Respiratory Syncytial Virus (RSV)
  • Respiratory syncytial virus is probably the most
    common cause of viral respiratory disease in
    infants
  • RSV is an RNA virus, member of Paramyxoviridae
    family, genus Pneumovirus
  • RSV replication occur initially in epithelial
    cells of the nasopharynx ? spread into the lower
    repiratory tract and cause bronchiolitis and
    pneumonia
  • The symptoms are coughing and wheezing that last
    for more than a week
  • The most recent approved treatment humanized
    monoclonal antibody, Palivizumab (Synagis)

47
RSV
BRONCHIOLITIS
48
Influenza (Flu)
  • History of influenza
  • 412 BC - first mentioned by Hippocrates
  • 1580 - first pandemic described
  • 1580-1900 - 28 pandemics

49
Pandemic influenza in the 20th Century
1918 Spanish Flu
1957 Asian Flu
1968 Hong Kong Flu
20-40 million deaths
1 million deaths
1 million deaths
H2N2
H3N2
H1N1
1920 1940 1960 1980 2000
50
Influenza Virus
  • Family Orthomyxoviridae
  • Three main types
  • Type A
  • Multiple species
  • Type B
  • Humans
  • Type C
  • Humans and swine
  • 15 HA and 9 NA for influenza A
  • All in aquatic birds
  • Hemagglutinin (HA)
  • Function Sites for attachment to infect host
    cells
  • Neuraminidase (NA)
  • Function Remove neuraminic acid from mucin and
    release from cell

51
Influenza A Virus
  • Antigenic drift
  • Changes in proteins by genetic point mutation
    selection
  • Immune response no longer protects fully
  • Ongoing and basis for change in vaccine each year
  • Antigenic shift
  • Changes in proteins through genetic reassortment
  • Produces different viruses not covered by annual
    vaccine
  • pre-existing antibodies do not protect
  • may get pandemics

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53
AGE SHIFTS IN MORTALITY
  • Concept of The Doctrine of Original Antigenic
    Sin, by Thomas Francis (1960) - immune response
    is greatest to antigens to which first exposure
    occurred in childhood.
  • Persons born before 1957 who were exposed in
    childhood to influenza A (H1N1) viruses might be
    better protected against this viral subtype than
    those who were first exposed to other influenza A
    subtypes, H2N2 and H3N2, at a later date .

54
Ecology of Influenza Virus A
55
Avian Influenza
  • Avian Influenza is an infection caused by avian
    (bird) influenza (flu) viruses
  • Flu viruses occur naturally among birds worldwide
  • Wild birds carry the viruses in their intestines,
    but usually do not get sick
  • Easily transmitted to domesticated birds like
    chickens, ducks, and turkeys and usually acquire
    them by coming in contact with contaminated
    excretionsthey usually die.
  • May be transmitted to other species
  • May mutate to cause human to
  • human infections
  • gt300 million domestic poultry culled
  • 186 human cases/ 105 fatalities
  • 24 March
    06

56
REASSORTMENT
57
Sebaran reseptor a2-3 atau a2-6 sialic acids
pada saluran pernafasan manusia Influenza virus
Receptors in Human air way, Nature vol. 440, 23
March 2006
a2-3
a2-6
b. Paranasal sinus
b
a
c
d
e
f
g
g. Alveolus
58
Novel Influenza A (H1N1) 2009 Virus ? SWINE FLU
  • New strain of A (H1N1)
  • Not previously detected in swine or human
  • Unusual mix of genetic segments including of
    swine, avian and human influenza viruses
  • Originated from pigs and at some point of time
    transmitted to human
  • Cases began to appear from 17th March09 in
    Mexico with human to human transmission
  • No cases in swine population and no infections
    from pork. Pigs are responsible only for mutation
    of virus.

59
PIG THE CREATOR
60
Treatment Prevention
  • Amantadine and rimantadine are effective
    prophylactic and curative drugs against Influenza
    virus A
  • The NA inhibitors zanamivir and oseltamivir were
    approved in 1999 for tx both influenza A and B
  • Multivalent vaccines are available for the eldery
    and other high-risk group

61
Fungal Diseases of The Lower Respiratory System
  • Fungal spores are easily inhale they may
    germinate in the lower respiratory tract
  • The incidence of fungal diseases has been
    increaseing in recent years

62
Histoplasmosis
  • Histoplasma capsulatum causes a subclinical
    respiratory infection that only occasionally
    progresses to severe, generalized disease
  • The disease is acquired by inhalation of airborne
    conidia
  • Isolation of the fungus or identification in
    tissues sample is necessasry for diagnosis
  • Treatment Ampotericin B

63
Coccidioidomycosis
  • Inhalation of the airborne arthroconidia of
    Coccidioides immitis can result
    Coccidioidomycosis
  • Most cases are subclinical, but when there are
    predisposing factors such as fatigue and poor
    nutrition, a progressive disease resembling
    tuberculosis can result ? fever, coughing, weight
    loss occasionally fatal
  • Treatment Ampotericicn B

64
Pneumocystis Pneumonia
  • Pneumocystis jeroveci (formerly P.carinii) is
    sometimes found in healthy human lung
  • Pneumonia a common serious complication of AIDS
  • Treatment Co-trimoxazole

65
Blastomycosis (North American Blastomycosis)
  • Blastomyces dermatitidis is the causative agent
    of blastomycosis
  • The infection begins in the lungs and can spread
    to cause extensive abcesses
  • Treatment Amphotericin B

66
Aspergillosis
  • Many other opportunistic fungi may cause
  • respiratory disease
  • Aspergillus fumigatus can cause
  • Allergic bronchopulmonary aspergillosis
  • Aspergilloma in patients with pre-existing
  • lung disease ? mass of hyphae produce fungus
    ball
  • Disseminated aspergillosis

67
Aspergillosis
68
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