Download Chapter 6 -Respiratory Infections

R ESPIRATORY I NFECTIONS
I NFECTIONS OF THE R ESPIRATORY TRACT

Most common entry point for infections

Upper respiratory tract


nose, nasal cavity, sinuses, mouth, throat
Lower respiratory tract

Trachea, bronchi, bronchioles, and alveoli in the lungs
R ESPIRATORY
TRACT
P ROTECTIVE M ECHANISMS
Normal flora: Commensal organisms

Limited to the upper tract

Mostly Gram positive or anaeorbic

Microbial antagonist (competition)
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.
O THER P ROTECTIVE M ECHANISMS

Nasal hair, nasal turbinates

Mucus

Involuntary responses (coughing)

Secretory IgA

Immune cells
R ESPONSE TOWARDS FOREIGN
PARTICLES

Ventilatory flow

Cough

Mucociliary clearance mechanisms

Mucosal immune system
S ELECTED B ACTERIAL I NFECTIONS
Pharyngitis
Group A Strep - Streptococcus pyogenes
(Many viruses also cause this)
Pneumonia -
Streptococcus pneumoniae
Diphtheria -
Corynebacterium diphtheriae
Tuberculosis -
Mycobacterium tuberculosis
Whooping cough - Bordetella pertussis
D ISEASE OF UPPER RESPIRATORY
TRACT
1.
2.
E XAMPLES OF COMMON
INFECTIONS

Laryngitis

Streptococcal Pharyngitis

Scarlet Fever

Sinusitis

Diptheria

Otitis media

Advance stages – bacterial superinfection, mastoiditis,
meningitis and brain abscess
L ARYNGITIS

Most commomly upper respiratory viruses

Diphtheria
- C. diphtheriae produces a cytotoxic exotoxin
causing tissues necrosis at site of infection with
associated acute inflammation. Membrane may
narrow airway and/ or slough off (asphyxiation)
S TREPTOCOCCAL
P HARYNGITIS (S TREP
T HROAT )

Caused by group A beta-hemolytic streptococci
of S.pyogenes

Also causing impetigo, erysipelas and
endocarditis on skin

Causing inflammation of the mucous membrane
and fever; tonsilitis and otitis media may also
occur

Rapid diagnosis using enzyme immunoassays.
S TREP T HROAT

Fever

Tonsillitis

Enlarged lymph
nodes

Middle-ear
infection
R EDDENING
OF THROAT
S TREPTOCOCCUS PYOGENES

Gram positive
streptococci

Carried and
transmitted from the
throat

In Respiratory
secretions
G ROUP A S TREP
The M protein has many antigenic varieties
and thus, different strain of S.pyogenes
cause repeat infections

Capsule -resistant to
phagocytosis

Enzymes damage
host cells

M protein adhesin
E NZYME
IMMUNOASSAYS
S CARLET
FEVER

Caused by S. pyogenes producing erythrogenic
toxin

The bacteriophage disturb the normal
characterristic of bacteria that involving genetic
mutation

Also associate with pharyngitis and skin infection
that caused by the same bacteria

It is nowadays become mild and rare disease
S CARLET F EVER
Caused by Erythrogenic
Toxin secreted by
S. pyogenes
S CARLET F EVER

The erythrogenic
toxin is coded by a gene
lysogenic bacteriophage
within the genome of
S. pyogenes

Rash is an inflammatory reaction to the toxin
S INUSITIS

Commonly caused by S. pneumoniae, Moraxella
catarrhalis / H. influezae

can also caused by S. aureus / S.pyogenes

The sinus cavity will swelling and prevent
drainage that resulting pressure and severe pain

Pt usually produce mucus, bacteria and
phagocytic cells that collect in the sinuses
C ONT.

Chronic stages caused by Bacteriodes

Mostly occur above the root of upper teeth
which infection derived from oral cavity

Treatment by applying moist heat on particular
area / drop an ephedrine / raise head to help
drainage

Best antibiotic - penicillin
S INUSITIS
D IPTERIA

Until 1935, it leading infection to children of US

Vaccine used for children is DTaP vaccine

Diptheria Toxoid antibodies Production (DTaP)

Spread thru air bourne and resistant towards
drying

The greyish toungue contain fibrin, dead tissues
and bacterial cells that block the air passage

0.01mg of highly virulence toxin - fatal
C ORYNEBACTERIUM
DIPHTHERIAE
 Aerobic Gram + bacillus
 Toxin inhibits protein synthesis of
cells to which it binds
 Destroyed cells and WBC form
"pseudomembrane" which blocks
airways
S EVERE
STAGE
U NDER MICROSCOPIC
OBSERVATION
C ORYNEBACTERIUM

To produce toxin, C. dithpheriae must
be infected with a bacteriophage
carrying the toxin gene
DIPHTHERIAE
G REY
MEMBRANE
T HE D IPHTHERIA O UTBREAK OF N OME ,
A LASKA , 1925
Heroic Alaska Dog Teams
A N “AB” TOXIN

B = binding subunit

A = active subunit
which binds to and
inhibits a eucaryotic
ribosomal translation
factor

Vaccine is diphtheria
toxoid
O TITIS
MEDIA

Uncomfortable common cold, that infecting nose
or throat (otitis media)

85% infecting children below 3 yrs old

Best antibiotic from penicillin group

The antibiotics used were just reduction the
duration of infection
CAUSES

S. pneumoniae

H. influenzae

S.pyogene

Moraxella catarrhalis

S.aureus
I NFECTED
M IDDLE
E AR
( OTITIS
MEDIA )
D ISEASES OF LOWER RESPIRATORY
TRACT
1.
2.
3.
W HOOPING COUGH
B ORDETELLA
PERTUSSIS

Gram negative coccobacillus

Capsule

Adherence to ciliated
cells

Pertussis toxin is A-B
toxin
P ERTUSSIS (W HOOPING C OUGH )

Cough

Violent coughing
followed by whooping
sound

Vaccine – it is made of
purified components

Not lifelong immunity –
adult carriers
P NEUMONIA
B ACTERIAL P NEUMONIA
Bacterial, viral or fungal infection can cause
Inflammation of the lung with fluid filled alveoli
C OMMUNITY A CQUIRED
P NEUMONIA

Infection of the lung parenchyma in a person
who is not hospitalized or living in a long-term
care facility for ≥ 2 weeks

5.6 million cases annually in the U.S.

Estimated total annual cost of health care = $8.4
billion

Most common pathogen = S. pneumo (60-70% of
CAP cases)
“N OSOCOMIAL ” P NEUMONIA

Hospital-acquired pneumonia (HAP)


Occurs 48 hours or more after admission, which
was not incubating at the time of admission
Ventilator-associated pneumonia (VAP)

Arises more than 48-72 hours after endotracheal
intubation
“N OSOCOMIAL ” P NEUMONIA

Healthcare-associated pneumonia (HCAP)


Patients who were hospitalized in an acute
care hospital for two or more days within 90
days of the infection; resided in a nursing
home or LTC facility; received recent IV abx,
chemotherapy, or wound care within the
past 30 days of the current infection; or
attended a hospital or hemodialysis clinic
Guidelines for the Management of Adults
with HAP, VAP, and HCAP. American
Thoracic Society, 2005
PATHOGENESIS

Inhalation, aspiration and hematogenous spread are
the 3 main mechanisms by which bacteria reaches
the lungs

Primary inhalation: when organisms bypass normal
respiratory defense mechanisms or when the Pt
inhales aerobic GN organisms that colonize the upper
respiratory tract or respiratory support equipment
PATHOGENESIS

Aspiration: occurs when the Pt aspirates
colonized upper respiratory tract secretions


Stomach: reservoir of GNR that can ascend,
colonizing the respiratory tract.
Hematogenous: originate from a distant source
and reach the lungs via the blood stream.
PATHOGENS

CAP usually caused by a single organism

Even with extensive diagnostic testing, most
investigators cannot identify a specific etiology
for CAP in ≥ 50% of patients.

In those identified, S. pneumo is causative
pathogen 60-70% of the time
S TREPTOCOCCUS PNEUMONIA

Most common cause of CAP

Gram positive diplococci

“Typical” symptoms (e.g. malaise, shaking chills,
fever, rusty sputum, pleuritic hest pain, cough)

Lobar infiltrate on CXR

Suppressed host

25% bacteremic
ATYPICAL P NEUMONIA

#2 cause (especially in younger population)

Commonly associated with milder Sx’s:
subacute onset, non-productive cough, no
focal infiltrate on CXR

Mycoplasma: younger Pts, extra-pulm Sx’s
(anemia, rashes), headache, sore throat

Chlamydia: year round, URI Sx, sore throat

Legionella: higher mortality rate, waterborne outbreaks, hyponatremia, diarrhea
V IRAL P NEUMONIA

More common cause in children

RSV, influenza, parainfluenza

Influenza most important viral cause in adults, especially
during winter months

Post-influenza pneumonia (secondary bacterial
infection)

S. pneumo, Staph aureus
O THER

Anaerobes



BACTERIA
Aspiration-prone Pt, putrid sputum, dental disease
Gram negative

Klebsiella - alcoholics

Branhamella catarrhalis - sinus disease, otitis, COPD

H. influenza
Staphylococcus aureus

IVDU, skin disease, foreign bodies (catheters,
prosthetic joints) prior viral pneumonia
S TREPTOCOCCUS
PNEUMONIAE

Pneumococcus

Encapsulated

Often secondary
infection following
influenza virus
B ACTERIAL P NEUMONIA
Streptococcus pneumoniae
• 2/3 of all pneumonia
• Risk Factors- old age, season, underlying
viral infection, diabetes, alcohol and narcotic
use
• Variable capsular antigen
• Purified component (capsule) vaccine
Others that cause pneumonia:
Mycoplasma pneumoniae
Legionella pneumophila
T UBERCULOSIS
M YCOBACTERIUM TUBERCULOSIS

Acid-fast bacillus – complex cell wall with “cord factor”

Causes TB: lungs
bones, other organs

Airborne, (milk, v. rare)
M YCOBACTERIUM

TUBERCULOSIS
Thick lipid coat
of “Mycolic fatty acids”

Grows very slowly

Resists killing by
macrophages and grows
in them
T UBERCULE FORMATION
A tubercle in the lung is a
“granuloma”
consisting of a central core of TB
bacteria inside an enlarged
macrophage, and an outer wall
of fibroblasts, lymphocytes,
and neutrophils
T UBERCULOSIS

Primary


Secondary (reactivation)


Lung tubercles, caseous, tuberculin skin reaction
Consumption: Coughing and chronic weight loss
Dissemination

Extrapulmonary TB (lymph nodes, kidneys,
bones, genital tract, brain, meninges)
T UBERCULOSIS
Elimination requires long antibiotic
treatment with “cocktail” of
antibiotics because
of the resistance that develops.
M ULTI -D RUG R ESISTANT
M YCOBACTERIUM
TUBERCULOSIS
TB S KIN T EST
H OW D OES T UBERCULOSIS
D EVELOP ?
 There
are two possible ways a
person can become sick with
TB disease:
 The
first applies to a person
who may have had been
infected with TB but is
perfectly healthy. The person
can get infected again if they
have a another disease such as
HIV or cancer or they may
get infected if they use
drugs/alcohol.
 The
other way it TB can
develop, happens much
more quickly. Sometimes
when a person first
breathes in the TB germs,
the body is unable to
protect itself against the
disease. The germs then
develop into active TB
disease within weeks.
W HO G ETS T UBERCULOSIS ?
Anyone can get tuberculosis. Some people are at
higher risks than others. The people who have
more of a chance getting TB are:

People who share same breathing space

Poor people/homeless people

Prisoners

Alcoholics or Drug users

People with medical conditions (cancer, diabetes)

Specially people with aids
P RIMARY TUBERCULOSIS
PNEUMONIA

This is an uncommon type of TB as pneumonia is
infectious. People who have it, have high fevers
and productive coughs. It occurs most often in
extremely young children and the elderly. This
type is also found in HIV and Aids infected
people.
T HE T HREE S TAGES

There are three stages in the disease of
tuberculosis. These three stages are identified
from mild to extreme danger which is death. The
first mild stage can get cured easily as long as the
patient gets medication on time and takes good
care. The second stage is more dangerous and the
patient has to be really careful and that is were
the symptoms should be considered. The third
stage is extremely dangerous and there is no cure
which means death. The third stage is the stage
were nothing should go wrong and the patient
will slowly begin to vomit blood and eventually
die.
W HO D ISCOVERED
T UBERCULOSIS ?

In 1882, Robert Koch discovered TB and
soon he found out that it was caused by a
microorganism Mycobacterium
tuberculosis. After discovering that this
disease was infectious, he started to
consider treatments. Many treatments
were tried but none were discovered until
the year of 1943 were the activity of
streptomycin was discovered.
V IRUS
INFECTIONS

Respiratory syncytial virus (“RSV”)

Influenza virus
Fungal Infections
•Coccidiodomycosis (Valley Fever)
Coccidioides immitis
T HE
COMMON COLD

Also known as coryza

Caused by viral infection

Show symptoms as other cold but secretion
might consist of pus and blood mucus

Leads to 2ndary infection – sinusitis, bronchitis
and otitis media

In serious case – likely as whooping cough and
respiratory
R ESPIRATORY S YNCYTIAL V IRUS

Enveloped (membrane) RNA virus

Spread by respiratory droplets

Community outbreaks in late fall to spring

Upper respiratory tract infection – epithelial cells

May be fatal in infants
I NFLUENZA V IRUS
A N ENVELOPED RNA VIRUS
Structure
Influenza Virus
New human strains every year
• Mutations
Pandemic strains

Genetic Recombinant Viruses
•1957 Asian Flu
H2N2
•1968 Hong Kong Flu H3N2
•1977 Russian Flu
H1N1
Bird Flu
Directly from birds
•??
H5N1
‘H’
AND
‘N’ F LU G LYCOPROTEINS
H – Hemagglutinin

• Specific parts bind to host
cells of the respiratory mucosa
• Different parts are
recognized by the host antibodies
• Subject to changes
N - Neuraminidase
• Breaks down protective
mucous coating
• Assist in viral release
I NFLUENZA

Epidemics and pandemics, mostly in
winter

Upper respiratory tract infection –
epithelial cells

Multivalent killed virus vaccine with strains
from the previous year (Grown in
embryonated eggs)

Bird flu (H5N1) pandemic in birds
C OCCIDIOIDES

Soil fungus in
American
Southwest

Cause of Valley
Fever

Highly infectious
IMMITIS
C OCCIDIOIDES
IMMITIS
L IFE C YCLE
C OCCIDIOIDES IMMITIS

Valley Fever usually a flulike illness

Can spread to bones, skin,
meninges

100,000 new cases/yr in
SW