 Most common place for infectious agents to

gain access to the body

 Upper respiratory tract: mouth, nose, nasal
cavity, sinuses, pharynx, epiglottis, larynx
 Lower respiratory tract: trachea, bronchi,
bronchioles, lungs, alveoli
 Defneses
› Nasal hair
› Cilia
› Mucus
› Involuntary responses such as coughing, sneezing,
and swallowing
› Macrophages
› Secretory IgA against specific pathogens
Figure 21.1
 Upper respiratory tract
Nasooropharyn Gram+ Neisseria spec.
x Gram- anaerobes a-hemolytic
streptococci
Haemophilus spec.

 Lower respiratory tract

› Mucociliary escalator
› Scarcely populated

4
 Generally limited to the upper respiratory tract
 Gram-positive bacteria (streptococci and
staphylococci) very common
 Disease-causing bact4eria are present as
normal biota; can cause disease if their host
becomes immunocompromised or if they are
transferred to other hosts (Streptococcus
pyogenes, Haemophilus influenza,
Streptococcus pneumonia, Neisseria
meningitides, Staphylococcus aureus)
 Normal biota perform microbial antagonism
 Rhinitis, or the Common Cold
› Symptoms: sneezing, scratchy throat, runny
nose (rhinorrhea)
› Symptoms begin 2-3 days after infection
› Generally not accompanied by fever
 Over 200 different viruses capable of
causing common cold
 Rhinoviruses (50%, over 100 serotypes)
 A single virus attached to mucosa might be
sufficient to cause a cold
 Coronaviruses (15-20%)
 Less frequent in older people
 Possibly accumulated immunity
 Duration ~1 week
 With remedies ~ 7 days

9
› Commonly called a sinus infection
› Most commonly caused by allergy
› Can also be caused by infections or structural
problems
› Generally follows a bout with the common cold
› Symptoms: nasal congestion, pressure above
the nose or in the forehead, feeling of
headache or toothache
› Facial swelling and tenderness common
› Discharge appears opaque with a green or
yellow color in case of bacterial infection
› Discharge caused by allergy is clear and may
be accompanied by itchy, watery eyes
 Also a common sequel of rhinitis
 Viral infections of the upper respiratory tract lead to
inflammation of the Eustachian tubes and buildup of
fluid in the middle ear- can lead to bacterial
multiplication in the fluids
 Bacteria can migrate along the eustachian tube
from the upper respiratory tract, multiply rapidly,
leads to pu production and continued fluid secretion
(effusion)
 Chronic otitis media: when fluid remains in the
middle ear for indefinite periods of time (may be
caused by biofilm bacteria)
 Symptoms: sensation of fullness or pain in the ear, loss
of hearing
 Untreated or severe infections can lead to eardrum
rupture
Figure 21.2
14
 More common in young children
 Small auditory tube which connects middle ear and
throat
 50% of all office visits to pediatrician
 S. pneumoniae (35%)
 H. influenzae (20-30%)
 M. catarrhalis (10-15%)
 S. pyogenes (8-10%)
 S. aureus (1-2%)
 Incidence of S. pneumoniae reduced by
vaccineby 6 – 7%
16
 Inflammation of the throat
 Pain and swelling, reddened mucosa,
swollen tonsils, sometime white packets
of inflammatory products
 Mucous membranes may swell, affecting
speech and swallowing
 Often results in foul-smelling breath
 Incubation period: 2-5 days
Figure 21.3
Figure 21.5
 Streptococcus pyogenes
› Group A streptococci
 Resistant to phagocytosis
 Streptokinases lyse clots
 Streptolysins are
cytotoxic
 Diagnosis
› indirect agglutination
› ELISA

21
 Include only S. pyogenes
 Group A streptococcal infections affect all ages
peak incidence at 5-15 years of age
 90% of cases of pharyngitis
 Structural components
› M protein M, which interferes with opsonization and lysis of
the bacteria
› Lipoteichoic acid & F protein adhesion
› Hyaluronic acid capsule, which acts to camouflage the
bacteria
 Enzymes
› Streptokinases facilitate the spread of streptococci through tissu
› Deoxynucleases
› C5a peptidase
 Pyrogenic toxins that stimulate macrophages and
helper T cells to release cytokines
 Streptolysins
› Streptolysin O lyse red blood cells, white blood cells, and
platelets
› Streptolysin S
 Suppurative
› Non-Invasive
 Pharyngitis (“strep throat”)-inflammation of the pharynx
 Skin infection, Impetigo
› Invasive
 Scarlet fever-rash that begins on the chest and spreads
across the body
 Pyoderma-confined, pus-producing lesion that usually
occurs on the face, arms, or legs
 Necrotizing fasciitis-toxin production destroys tissues and
eventually muscle and fat tissue
 Non Suppurative
› Rheumatic fever: Life threatening inflammatory
disease that leads to damage of heart valves
muscle
› Glomerulonephritits
 Immune complex disease of kidney
 inflammation of the glomeruli and nephrons which
obstruct blood flow through the kidneys
 Rheumatic Fever-autoimmune disease
involving heart valves,joints, nervous
system. Follows a strep throat
 Acute glomerulonehritis or Bright’s
Disease-inflamatory disease of renal
glomeruli and structures involved in
blood filter of kidney. Due to deposition
of Ag/Ab complexes
 Most common cause of permanent
heart valve damage in children
 Exact cause not yet known but there
appears to be some antibody cross
reactivity between the cell wall of S.
pyogenes and heart muscle
 Diagnosis is based on symptoms and is
difficult
 Occurs most frequently between ages of
6 and 15
 US it is about 0.05% of pop having strep
infections
 100x more frequent in tropical countries
 Treatment is via salicylates (aspirin
derivatives) and corticosteroids to
decrease inflammation and fever.
 Diagnosis based on history of Strep throat
and clinical findings.
 Symptoms include fever,
malaise,edema, hypertension and blood
or protein in urine
 Occurs in 0.5% of those having strep
throat.
 Penicillin or erythromycin to eradicate
and residual strep infection
 80-90% of cases recover with bed rest
lasting for months
 Kidney damage in the remainder is often
permanent resulting in chronic
glomerular nephritis
 The following tests can be used to differentiate
between -hemolytic streptococci
› Lanciefield Classification
› Bacitracin susceptibility Test
 Specific for S. pyogenes (Group A)
› CAMP test
 Specific for S. agalactiae (Group B)
 Principle:
› Bacitracin test is used for
presumptive identification of group
A
› To distinguish between S. pyogenes
(susceptible to B) & non group A such
as S. agalactiae (Resistant to B)
› Bacitracin will inhibit the growth of gp
A Strep. pyogenes giving zone of
inhibition around the disk
 Procedure:
› Inoculate BAP with heavy suspension
of tested organism
› Bacitracin disk (0.04 U) is applied to
inoculated BAP
› After incubation, any zone of inhibition
around the disk is considered as
susceptible
 Principle:
› Group B streptococci produce extracellular protein (CAMP
factor)
› CAMP act synergistically with staph. -lysin to cause lysis of
RBCs

 Procedure:
› Single streak of Streptococcus to be tested and a Staph.
aureus are made perpendicular to each other
› 3-5 mm distance was left between two streaks
› After incubation, a positive result appear as an arrowhead
shaped zone of complete hemolysis
› S. agalactiae is CAMP test positive while non gp B
streptococci are negative
 Hemolysis Bacitracin CAMP test
sensitivity
S. pyogenes  Susceptible Negative

S. agalactiae  Resistant Positive

Figure 21.7
 Streptococcus pyogenes
 Pharyngitis + exanthem
› Erythrogenic toxin produced by lysogenized S.
pyogenes
 Tongue strawberry like

37
 Symptoms initially experienced in the
upper respiratory tract
 Sore throat, lack of appetite, low-grade
fever
 Pseudomembrane forms on the tonsils or
pharynx
 Corynebacterium diphtheriae
 Gram-positive rod, pleomorphic
 Diphtheria (Greek: leather) membrane forms in
throat
 fibrin, dead tissue, and bacteria
 Diphtheria toxin produced by lysogenized C.
diphtheriae
 Blocks protein biosynthesis
 Infection is local but toxin may spread systemically
 Kidney failure, heart failure
 Nerve damage  soft palata, eye muscles, extremities
 Prevented by DTaP and Td vaccine (Diphtheria
toxoid)

39
 Morphology

› Gram-positive, non–spore-forming
rods
› Arrange in palisades:
―L-V‖ shape; ―Chinese characters‖
› Pleomorphic: ―club-ends‖ or
coryneform
› Beaded, irregular staining
41
42
Figure 21.8
 Toxigenic Corynebacterium diphtheriae
› Worldwide distribution but rare in places where vaccination
programs exist
 Exotoxin, Diphtheria toxin, as the virulence factor
› Not all C. diphtheriae strains produce toxin
› Toxin is produced by certain strains
› Toxin is antigenic
 Toxin consists of two fragments
› A: Active fragment
 Inhibits protein synthesis
 Leads to cell/tissue death
› B: Binding
 Binds to specific cell membrane receptors
 Mediates entry of fragment A into cytoplasm of host cell
Figure 21.10
 Insidiousonset
 Exudate spreads within 2-3 days and
may form adherent membrane
 Membrane may cause respiratory
obstruction
 Pseudomembrane: fibrin, bacteria,
and inflammatory cells, no lipid
 Fever usually not high but patient
appears toxic
 Most attributable to toxin
 Severity generally related to extent of
local disease
 Most common complications are
myocarditis and neuritis
 Death occurs in 5%-10% for respiratory
disease
 Microscopic morphology
› Gram-positive, non–spore-
forming rods, club-shaped, can be
beaded
› Appear in palisades and give
"Chinese letter" arrangement
› Produce metachromatic granules
or ―Babes’ Ernst‖ bodies (food
reserves) which stain more darkly
than remainder of organism

Corynebacterium diphtheriae
gram stain
 Loeffler's slant or Pai's slant—
Used to demonstrate
pleomorphism and
metachromatic granules ("Babes’
Ernst bodies―)

 Growth on Serum Tellurite or

modified Tinsdale exhibits brown
or grayish→ to black halos
around the colonies

Tellurite: tellurium dioxide (TeO2).

 Blood agar plae (BAP) 24-48 hours at 37oC
small, grey translucent colonies
 Small zone of - hemolysis also s een
 Identification
› Confirm identification by fermentation reactions
(glucose +)
› Catalase positive
› Urease negative
› Non-motile
 Toxigenicity testing
› Elek test
› Immunodiffusion test
 Organisms are streaked on
media with low Fe content
to maximize toxin
production.
 Identification of C.
diphtheriae does NOT
mean the patient has
dipheria. Must show the
isolate produces the toxin.

protease peptone agar + serum (horse or bovine)

1 and 4 positive
 Produced in horses
 First used in the U.S. in 1891
 Used only for treatment of diphtheria
 Neutralizes only unbound toxin
 Lifetime of Ab: 15 days – 3 weeks, wait 3-
4 weeks before giving toxoid. Only given
once.
 Reservoir Human carriers
Usually asymptomatic

 Transmission Respiratory, aerosols

Skin lesions

 Temporal pattern Winter and spring

 Communicability Up to several weeks

without antibiotics
 20000
18000
16000
14000
12000
Cases

10000
8000
6000
4000
2000
0
1940 1950 1960 1970 1980 1990 2000

Year
 6

4
Cases

0
1980 1985 1990 1995 2000 2005
Year
 25

20
Cases

15

10

0
<5 5-14 15-24 25-39 40-64 65+
Age group (yrs)
N=53
 Formalin-inactivated diphtheria toxin
 Schedule Three or four doses + booster
Booster every 10 years
 Efficacy Approximately 95%
 Duration Approximately 10 years
 Shouldbe administered with tetanus
toxoid as DTaP, DT, Td, or Tdap
Dose Age
Primary 1 2 months
Primary 2 4 months
Primary 3 6 months
Primary 4 15-18 months

4-6 yrs
11-12 yrs
Every 10 yrs
 A number of infectious agents affect
both the upper and lower respiratory
tract regions
 Most well-known: whopping cough,
respiratory syncytial virus (RSV), and
influenza
 Also known as pertussis
 Two distinct symptom phases
› Catarrhal stage
 After incubation from 3 to 21 days
 Bacteria in the respiratory tract cause what appear to
be cold symptoms (runny nose)
 Lasts 1 to 2 weeks
› Paroxysmal stage
 Severe and uncontrollable coughing
 Violent coughing spasms can result in burst blood
vessels in the eyes or even vomiting
 Followed by a long recovery (convalescent)
phase
› Complete recovery requires weeks or even months
› Other microorganisms can more easily cause
secondary infection
65
66
 Highly
contagious respiratory infection
caused by Bordetella pertussis
 Outbreaks first described in 16th
century
 Bordetella pertussis isolated in 1906
 Estimated 294,000 deaths worldwide
in 2002
 Primarily a toxin-mediated disease
 Bacteria attach to cilia of respiratory
epithelial cells
 Inflammation occurs which interferes
with clearance of pulmonary
secretions
 Pertussis antigens allow evasion of host
defenses (lymphocytosis promoted but
impaired chemotaxis)
 Reservoir Human
Adolescents and adults

 Transmission Respiratory droplets

 Communicability Maximum in catarrhal

stage
Secondary attack rate
up to 80%
Pertussis—United States, 1940-2005

250000

200000

150000
Cases

100000

50000

0
1940 1950 1960 1970 1980 1990 2000

Year
Pertussis—United States, 1980-2005

30000

25000

20000
Cases

15000

10000

5000

0
1980 1985 1990 1995 2000 2005

Year
 DTaP (pediatric)
› approved for children 6 weeks through 6
years (to age 7 years)
› contains same amount of diphtheria and
tetanus toxoid as pediatric DT
 Tdap (adolescent and adult)
› approved for persons 10-18 years (Boostrix)
and 11-64 years (Adacel)
› contains lesser amount of diphtheria toxoid
and acellular pertussis antigen than DTaP
 Stage 1:
Catarrhal stage,
like common
cold
 Stage 2:
Paroxysmal
stage: Violent
coughing sieges
 Stage 3:
Convalescence
stage http://www.vaccineinformation.org/photos/pert_wi001.j
pg

73
 Major complications most common among
infants and young children
 Include hypoxia, apnea, pneumonia,
seizures, encephalopathy, and malnutrition
 Young children can die from pertussis
 Most deaths occur among unvaccinated
children or children too young to be
vaccinated

 Prevented by DTaP vaccine (acellular

Pertussis cell fragments)
74
Figure 21.26