Transcript RESPIRATORY TRACT INFECTIONS

RESPIRATORY
TRACT
INFECTIONS
Department of Microbiology
Faculty of Medicine
Brawijaya University
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 :
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 nose,
nasal cavity, sinuses, throat and
associated structures such as the middle
ear and auditory tube
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Lower respiratory tract
 Trachea,
bronchi, bronchioles, and alveoli
in the lungs
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
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.
Other Protective Mechanisms
Nasal hair, nasal turbinates
 Mucus
 Involuntary responses (coughing)
 Secretory IgA
 Immunocompetent cells
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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
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Bacterial Diseases of The Upper
Respiratory System
Streptococcal Pharyngitis (Strep Throat)
 Scarlet Fever
 Otitis Media
 Diphteria
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Streptococcal Pharyngitis
(Strep Throat)
This infection is caused by group A betahemolytic streptococci (Streptococcus
pyogenes)
 Gram positive cocci, katalase : negative
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Streptococcus pyogenes
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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
Strep Throat
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Fever
Tonsillitis
Enlarged lymph
nodes
Middle-ear infection
Treatment :
Antibiotic  Penicillin
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)
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Scarlet Fever
Caused by Erythrogenic
Toxin secreted by
S. pyogenes
Scarlet Fever
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The erythrogenic
toxin is coded by a gene
lysogenic bacteriophage
within the genome of
S. pyogenes
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Rash is an inflammatory reaction to the toxin
Infected
Middle
Ear
(otitis
media)
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
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Diphtheria
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
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Corynebacterium diphtheriae
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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
Corynebacterium diphtheriae
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To produce exotoxin,
C. diphtheriae must be
infected with a
bacteriophage carrying
the toxin gene
An “AB” toxin
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B = binding subunit
A = active subunit
which binds to and
inhibits a eucaryotic
ribosomal translation
factor
Vaccine is diphtheria
toxoid
Diphtheria
Diphtheria
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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
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
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
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
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Bacterial Diseases of The Lower
Respiratory System
Bacterial Pneumonias
 Pertussis (Whooping Cough)
 Tuberculosis  (module)
 Melioidosis
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Bacterial Pneumonias
Typical Pneumonia is caused by
Streptococcus pneumoniae
(= Diplococcus pneumoniae =
Pneumococcus)
 Atypical Pneumonias are caused by other
microorganisms
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Pneumococcal Pneumonia
Pneumococcal Pneumonia
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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
Haemophilus influenzae
Pneumonia
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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.influenza
strains
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
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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
Legionellosis
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This disease is caused by aerobic gramnegative rod Legionella pneumophila
The bacterium can grow in water, such as airconditioning 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
Psittacosis (Ornithosis)
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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
Chlamydial Pneumonia
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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 pearshaped appearance
Suggesting that C.pneumoniae associated with
atherosclerotic coronary artery and cvd
Tetracycline is used for treatment
Chlamydia pneumoniae
Q Fever
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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
Melioidosis
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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
Pertussis (Whooping Cough)
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Pertussis is caused by Bordetella pertussis
B.pertussis is a small, obligately aerobic gramnegative 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
Pertussis (Whooping Cough)
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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
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
Respiratory Syncytial Virus (RSV)
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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)
RSV
BRONCHIOLITIS
Influenza (Flu)
History of influenza
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412 BC - first mentioned by
Hippocrates
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1580 - first pandemic
described
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1580-1900 - 28 pandemics
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
Influenza Virus
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Family
Orthomyxoviridae
Three main types
 Type
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C
Humans and swine
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All in aquatic birds
Hemagglutinin (HA)
B
Humans
 Type
15 HA and 9 NA for
influenza A
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Multiple species
 Type
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A
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Function: Sites for
attachment to infect host
cells
Neuraminidase (NA)
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Function: Remove
neuraminic acid from mucin
and release from cell
Influenza A Virus
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Antigenic drift
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Changes in proteins by
genetic point mutation &
selection
 Immune response no longer
protects fully
 Ongoing and basis for change
in vaccine each year
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Antigenic shift
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Changes in proteins through
genetic reassortment
 Produces different viruses not
covered by annual vaccine
 pre-existing antibodies do not
protect
 may get pandemics
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 .
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Ecology of Influenza Virus A
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 excretions—they usually die.
 May be transmitted to other species
 May mutate to cause human to
human infections
 >300 million domestic poultry culled
 186 human cases/ 105 fatalities
24 March 06
REASSORTMENT
Sebaran reseptor α2-3 atau α2-6 sialic acids pada saluran pernafasan manusia
Influenza virus Receptors in Human air way,
Nature vol. 440, 23 March 2006
c. Pharynx
α2-3 α2-6
b. Paranasal sinus
ab
c
d. Trachea
e. Bronchus
d
e
f
f. Bronchiole
g. Alveolus
g
Novel Influenza A (H1N1) 2009 Virus
 SWINE FLU
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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 March’09 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.
PIG THE CREATOR
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
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Fungal Diseases of The Lower
Respiratory System
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Fungal spores are easily inhale ; they may
germinate in the lower respiratory tract
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The incidence of fungal diseases has been
increaseing in recent years
Histoplasmosis
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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
Coccidioidomycosis
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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
Pneumocystis Pneumonia
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Pneumocystis
jeroveci (formerly
P.carinii) is
sometimes found in
healthy human lung
Pneumonia; a
common serious
complication of AIDS
Treatment : Cotrimoxazole
Blastomycosis (North American
Blastomycosis)
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Blastomyces dermatitidis is
the causative agent of
blastomycosis
The infection begins in the
lungs and can spread to
cause extensive abcesses
Treatment : Amphotericin B
Aspergillosis
Many other opportunistic fungi may cause
respiratory disease
Aspergillus fumigatus can cause:
 Allergic bronchopulmonary aspergillosis
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Aspergilloma: in patients with pre-existing
lung disease  mass of hyphae produce fungus ball
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Disseminated aspergillosis
Aspergillosis