Respiratory Tract Infections

John Santangelo
2011
Upper
Lower
Upper Respiratory infections
1. Streptococcus pyogenes
2. Haemophilus influenzae
3. Staphylococcus aureus
4. Streptococcus pneumoniae
5. Diphtheria
Lower Respiratory infections
1. Streptococcus pneumoniae
2. Klebsiella pneumoniae
3. Staphylococcus aureus
4. Streptococcus pyogenes
5. Haemophilis influenzae
6. Myobacterium tuberculosis (galloping consumption)
7. Bordetella pertussis
8. Mycoplasma pneumoniae
9. Coxiella burnetti
10.Chlamydia psittaci
Streptococci are a large and diverse group of gram-positive
cocci that grow in pairs or chains.
Streptococcus pyogenes (a group A Streptococcus) is a
ubiquitous organism that is known to provoke a wide variety of
diseases in humans.
Group A streptococci (GAS) are gram-positive, nonmotile,
non–spore-forming organisms that appear as pairs or short-to-
moderate–sized chains.
The individual organism is spheric or ovoid and has a diameter
of 0.6-1 µm.
The cultures on blood agar plates appear as white-to-gray
colonies 1-2 mm in diameter surrounded by zones of complete
hemolysis.
Some colonies produce large amounts of hyaluronic acid,
which appears mucoid on the culture plate.
 Spectrum of diseases from group A
streptococcal infections
In the pre antibiotic era, streptococci frequently caused
significant morbidity and mortality.
in the post antibiotic period, diseases from streptococcal
infections are well controlled and uncommonly cause death.
The streptococci not only cause acute infections but are also
responsible for non suppurative postinfectious sequelae such as
rheumatic fever and glomerulonephritis.
Pharyngitis and impetigo are the common streptococcal
infections.
 The suppurative (Pus forming) complications of Group A
Streptococcus tonsillopharyngitis include the following:
• Tonsillopharyngeal cellulitis or abscess
• Otitis media
• Sinusitis
• Necrotizing fasciitis (Flesh eating disease)
• Streptococcal bacteremia
• Meningitis or brain abscess (rare complication resulting
from direct extension of an ear or sinus infection or from
bacteremic spread).
The non suppurative (Non Pus forming) complications of GAS
tonsillopharyngitis include the following:
• Acute rheumatic fever
• Acute glomerulonephritis
• Streptococcal toxic shock syndrome (strep TSS)
Many strains of streptococci have a predilection for the upper
respiratory tract.
Multiple factors influence virulence and initiation of infection in
the host.
The streptococcal cell wall is resistant to degradation and may
persist indefinitely in the tissues.
 The organism adheres to the mucous membranes via the
lipoteichoic acid (LTA) that is present on the cell wall of
streptococci.
LTA is cytotoxic and is capable of several different biological
activities.
Once adherence has occurred, the streptococci resist
phagocytosis, proliferate, and begin to invade the local tissues.
Most strains of Group A Streptococcus produce 2 haemolytic
toxins:
Streptolysin O and Streptolysin S.
Streptolysin is toxic to a variety of cells, including
polymorphonuclear leukocytes, platelets, and tissue culture
cells.
Measurement of antistreptolysin O antibodies in humans is
used as an indicator of recent streptococcal infection. ASOT
Pyrogenic exotoxins
Group A Streptococcus produce 3 different types of exotoxins
(ie, A, B, C).
These toxins are responsible for causing fever and scarlet
fever rash.
Additionally, these exotoxins increase susceptibility to
endotoxic shock, cause dysfunction of the reticuloendothelial
system, produce cardiac and hepatic necrosis in animals, and
depress antibody synthesis.
These toxins serve as immunomodulators of the host defense
system because they stimulate T cells to proliferate and are
referred to as super antigens.
 Group A Streptococcus release a large number of proteins
into the external environment.
Two different types of streptokinase are released.
The streptokinase forms a complex with plasminogen activator
and catalyzes the conversion of plasminogen to plasmin, thus
leading to digestion of fibrin.
Acute rheumatic fever (ARF)
ARF is a delayed non suppurative sequela of a pharyngeal
infection with Group A Streptococcus.
Following the initial pharyngitis, a latent period of 2-3 weeks
occurs before the first signs or symptoms of ARF appear.
The disease might present with a combination of clinical
manifestations that may include arthritis, carditis, chorea,
subcutaneous nodules, and erythema marginatum.
Poststreptococcal glomerulonephritis
Poststreptococcal glomerulonephritis is caused by infection with
specific nephritogenic strains of Group A Streptococcus (type
12 and type 49) and might occur in sporadic cases or during
an epidemic.
The incidence of glomerulonephritis in children is approximately
5-10% with pharyngitis and 25% with skin infections.
Tonsillopharyngeal cellulitis or abscess
Streptococcal pharyngitis might lead to cellulitis or an abscess
in the peritonsillar or retropharyngeal spaces.
In these infections, Group A Streptococcus in association with
oral flora might be the culprit organisms.
Otitis media
One of the two most common suppurative complications of
streptococcal tonsillopharyngitis is caused by spread of
organisms via the eustachian tube.
However, Group A Streptococcus infections account for fewer
than 5% of overall cases of otitis media.
Sinusitis
Direct spread of organisms leads to sinusitis, a common
complication of streptococcal tonsillopharyngitis.
Acute sinusitis presents with persistent coryza, postnasal drip,
headache, and fever.
Tenderness can be elicited over the affected sinus.
Mortality/Morbidity
Group A Streptococcus bacteremia remains a serious
infection.
The mortality rate is 25-48%.
The clinical manifestations of Group A Streptococcus infection
vary and depend on the suppurative and non suppurative
complications.
Group A Streptococcus are the most common cause of acute
bacterial pharyngitis.
They can also cause a variety of cutaneous and invasive
infections (eg, pyoderma, erysipelas, cellulitis, necrotizing
fasciitis, myositis) and other complications (eg, rheumatic
fever, acute glomerulonephritis).
Erysipelas
St Anthony’s Fire
 Erysipelas
St Anthony’s Fire
cellulitis
Necrotizing fasciitis (Flesh eating disease)
 Rheumatic Valvulitis in Acute
Rheumatic Fever
Note the minute, firmly adherent
vegetations on the aortic valve cusps,
along the line of closure. These
vegetations, sometimes called "verrucae"
are composed of fibrin, and probably
represent friction damage of the inflamed
endocardium. These lesions rarely cause
functional problems, and usually resolve
after the acute episode of rheumatic
fever.

Chronic Rheumatic Valvulitis

The long-term sequelae of valvular
inflammation due to rheumatic fever is the
development of diffuse fibrosis of the valve
leaflets. The leaflets are thickened,
sometimes calcified, and the commisures
may be fused. This results in stenosis of
the valve. This view of the atrioventricular
valves shows marked stenosis and
calcification of the mitral valve, and less
severe involvement of the tricuspid valve.
The mitral and aortic valves are affected
more often than the tricuspid valve. The
pulmonary valve is only rarely affected.
Group A Streptococcus Pyogenes
Gram Stain Strep group A
 Haemophilus influenzae
Haemophilus influenzae is a small (1 µm X 0.3 µm), pleomorphic,
gram-negative coccobacillus.
It is a nonmotile, non–spore-forming, fastidious, facultative
anaerobe.
Some strains of H influenzae possess a polysaccharide capsule.
These strains are serotyped into 6 different types (a-f) based on
their biochemically different capsules.
Some strains have no capsule and are termed nonencapsulated H
influenzae or nontypeable H influenzae (NTHi).
The different strains can be identified with slide agglutination for
serotyping or polymerase chain reaction (PCR) for capsular
typing.
The most virulent strain is H influenzae type b (Hib), with its polyribosyl
ribitol phosphate (PRP) capsule.
It accounts for more than 95% of H influenzae invasive diseases in
children and half of invasive diseases in adults.
including bacteremia, meningitis, cellulitis, epiglottitis, septic arthritis,
pneumonia, and empyema.
Empyema is the presence of gross pus in the pleural cavity; it consists
of an effusion containing polymorphonuclear leukocytes and fibrin.
Empyema is caused by an infection that spreads from the lung and
leads to an accumulation of pus in the pleural space.
Less-common invasive Hib infections include endophthalmitis, urinary
tract infection, abscesses, cervical adenitis, glossitis, osteomyelitis, and
endocarditis.
Endophthalmitis is an inflammation of the internal coats of the eye. It is
a dreaded complication of all intraocular surgeries, particularly cataract
surgery, with possible loss of vision and the eye itself.
The other encapsulated strains H influenzae occasionally cause
invasive disease similar to that of Hib.
H influenzae type A (Hia) has been known to cause invasive
disease (eg, meningitis) clinically indistinguishable from that
caused by Hib.
The nonencapsulated, or NTHi, strains cause mucosal
infections, including otitis media, conjunctivitis, sinusitis,
bronchitis, and pneumonia.
Less commonly, these strains cause invasive disease in
children but account for half of the invasive infections in adults.
 H influenzae requires 2 erythrocyte factors for growth:
X (hemin) and V (nicotinamide-adenine-dinucleotide). NAD
These factors are released following lysis of red blood cells,
thereby allowing growth of this fastidious organism on
chocolate agar.
H influenzae consists of 8 biotypes;
biotype 3 (Haemophilus aegyptius) is associated with Brazilian
purpuric fever, and biotype 4 is a neonatal, maternal, and
genital pathogen.
Humans are the only natural hosts. NTHi strains are a
common resident of the nasopharyngeal mucosa and, in some
instances, of the conjunctivae and genital tract.
Transmission is by direct contact or by inhalation of respiratory
tract droplets.
Nasopharyngeal colonization of encapsulated H influenzae is
uncommon, occurring in 2-5% of children in the pre vaccine era
and even less after widespread vaccination.
The incubation period is not known.
A larger bacterial load or the presence of a concomitant viral
infection can potentiate the infection.
The colonizing bacteria invade the mucosa and enter the
bloodstream.
The presence of antibodies, complements, and phagocytes
determines the clearance of the bacteremia.
The antiphagocytic nature of the Hib capsule and the absence
of the anticapsular antibody lead to increasing bacterial
proliferation.
When the bacterial concentration exceeds a critical level, it can
disseminate to various sites, including meninges, subcutaneous
tissue, joints, pleura, pericardia, and lungs.
Newborns have a low risk of infection because of acquired
maternal antibodies.
When these transplacental antibodies to the PRP antigen wane,
infants are at high risk of developing invasive H influenzae
disease, and their immune responses are low even after the
disease.
Therefore, they are at high risk of repeat infections since prior
episodes of H influenzae do not confer immunity. By age 5
years, most children have naturally acquired antibodies.
Mortality/Morbidity
Overall mortality from Hib meningitis is approximately 5%.
Morbidity rates from meningitis, however, are high.
If subtle neurologic changes are included, as many as 50% of
individuals with Hib meningitis have some neurologic sequelae,
including partial-to-total sensorineural hearing loss,
developmental delay, language delay, behavioural abnormalities,
language disorders, impaired vision, mental retardation, motor
problems, ataxia, seizures, and hydrocephalus.
Approximately 6% of individuals with Hib meningitis experience
permanent sensorineural hearing loss.
Epiglottitis carries a mortality rate of 5-10% (because of acute
respiratory tract obstruction), and neonatal H influenzae disease
carries a mortality rate of 55%.
Race
The frequency of Hib disease is especially high in certain ethnic
groups, including African Americans, American Indians (eg,
Alaskan Eskimos, Navajo, Apache, Yakima, Athabaskan), and
Australian Aborigines.
Prior to availability of the Hib vaccine, the incidence of invasive
disease was 10% higher in American Indians and Alaskan
native children than the rest of the US population.
The rate of Hib disease among rural Alaskan native children is
high (5.4 per 100,000) despite Hib vaccination.
Sex
Hib disease has no sexual predilection; however, women are at
risk for postpartum sepsis, tuboovarian abscess, and chronic
salpingitis caused by NTHi that colonize the genital tract.
Age
• In general, Hib infections are rare in patients older than 6 years
because of the acquisition of secondary immunity; however,
immunocompromised individuals remain susceptible.
• Hib meningitis primarily affects children younger than 2 years,
with a peak frequency in infants aged 6-9 months.
Epiglottitis is most common in children aged 2-7 years but can
also occur in adults.
Hib pneumonia typically occurs in children aged 4 months to 4
years.
Hib causes septic arthritis and cellulitis in children younger than
2 years
NTHi causes neonatal sepsis through vertical transmission via the female


genital tract, maternal sepsis, and, infrequently, other invasive diseases. It

also causes otitis media, sinusitis, bronchitis, and pneumonia in all age
groups.
Lab Studies
• Gram stain: Test results on body fluids from various sites of
infection that reveal small, gram-negative, pleomorphic
coccobacilli with polymorphonuclear cells are strong evidence
of infection.
• Bacterial culture
• Detection of the organism in a blood culture or any other body
fluid is the most confirmatory method of establishing the
diagnosis.
• Seventy to 90% of patients with epiglottitis have positive
blood culture results.
However, to avoid laryngospasm, perform venipuncture and
cultures of the inflamed epiglottitis only after the airway has
been secured.
Antibiotics and supportive care
These are the mainstays of treatment.
Initially, invasive and serious H influenzae type b (Hib)
infections are best treated with an intravenous third-generation
cephalosporin until antibiotic sensitivities become available.
Haemophilus influenzae B (Hib) disease
Haemophilus influenzae Infection
Blood agar plate culture showing Haemophilus influenzae
satelliting around Staphylococcus aureus.
Staphylococcus aureus (Golden Staph)
The Staphylococci
Staphylococci are Gram-positive spherical bacteria that occur in
microscopic clusters resembling grapes.
Bacteriological culture of the nose and skin of normal humans
invariably yields staphylococci.
In 1884, Rosenbach described the two pigmented colony types of
staphylococci and proposed the appropriate nomenclature:
Staphylococcus aureus (yellow) and Staphylococcus albus
(white).
Staph Albus is now named Staphylococcus epidermidis.
Although more than 20 species of Staphylococcus are described
in Bergey's Manual (2001), only Staphylococcus aureus and
Staphylococcus epidermidis are significant in their interactions
with humans. S. aureus colonizes mainly the nasal passages, but
it may be found regularly in most other anatomical locales. S
epidermidis is an inhabitant of the skin.
Staphylococcus aureus forms a fairly large yellow colony on rich medium.
Staph epidermidis has a relatively small white colony.
S. aureus is often haemolytic on blood agar;

S. epidermidis is non hemolytic.

Staphylococci are facultative anaerobes that grow by aerobic respiration or
by fermentation that yields principally lactic acid.
The bacteria are catalase-positive and oxidase-negative.
S. aureus can grow at a temperature range of 15 to 45 degrees and at NaCl
concentrations as high as 15 percent.
Nearly all strains of S. aureus produce the enzyme coagulase: nearly all
strains of S. epidermidis lack this enzyme.
S. aureus should always be considered a potential pathogen; most strains
of S. epidermidis are non pathogenic and may even play a protective role in
their host as normal flora.
Staphylococcus epidermidis might be a pathogen in the hospital
environment.
Staphylococci are perfectly spherical cells about 1 micrometer
in diameter.
They grow in clusters because staphylococci divide in two
planes.
The configuration of the cocci helps to distinguish staphylococci
from streptococci, which are slightly oblong cells that usually
grow in chains (because they divide in one plane only).
The catalase test is important in distinguishing streptococci
(catalase-negative) from staphylococci, which are vigorous
catalase-producers.
The test is performed by adding 3% hydrogen peroxide to a
colony on an agar plate or slant. Catalase-positive cultures
produce O2 and bubble at once.

The test should not be done on blood agar because blood itself
contains catalase.
Pathogenesis of S. aureus infections
Staphylococcus aureus causes a variety of suppurative (pus-
forming) infections and toxinoses in humans.
It causes superficial skin lesions such as boils, styes and
furunculosis; more serious infections such as pneumonia,
mastitis, phlebitis, meningitis, and urinary tract infections; and
deep-seated infections, such as osteomyelitis and endocarditis.
S. aureus is a major cause of hospital acquired (nosocomial)
infection of surgical wounds and infections associated with
indwelling medical devices. S. aureus causes food poisoning by
releasing enterotoxins into food, and toxic shock syndrome by
release of super antigens into the blood stream.
Membrane-damaging toxins
a-toxin (a-hemolysin) The best characterized and most potent
membrane-damaging toxin of S. aureus is a-toxin.
In humans, platelets and monocytes are particularly sensitive to a-toxin.
ß-toxin is a sphingomyelinase which damages membranes rich in this lipid.
The classical test for ß-toxin is lysis of sheep erythrocytes. The majority of
human isolates of S. aureus do not express ß-toxin.
d-toxin is a very small peptide toxin produced by most strains of S. aureus. It is
also produced by S. epidermidis. The role of d-toxin in disease is unknown.
Leukocidin is a multi component protein toxin produced as separate
components which act together to damage membranes.
Coagulase is an extracellular protein which binds to prothrombin in the host to
form a complex called staphylothrombin.
The protease activity characteristic of thrombin is activated in the complex,
resulting in the conversion of fibrinogen to fibrin.
Coagulase is a traditional marker for identifying S aureus in the clinical
microbiology laboratory.
 Streptococcus pneumoniae
Streptococcus pneumoniae is a normal inhabitant of the human
upper respiratory tract.
The bacterium can cause pneumonia, usually of the lobar type,
paranasal sinusitis and otitis media, or meningitis, which is
usually secondary to one of the former infections.
It also causes osteomyelitis, septic arthritis, endocarditis,
peritonitis, cellulitis and brain abscesses.
Streptococcus pneumoniae is currently the leading cause of
invasive bacterial disease in children and the elderly.
Streptococcus pneumoniae is known in medical microbiology
as the pneumococcus, referring to its morphology and its
consistent involvement in pneumococcal pneumonia.
Pneumonia is a disease of the lung that is caused by a variety of bacteria
including Streptococcus, Staphylococcus, Pseudomonas, Haemophilus,
Chlamydia and Mycoplasma, several viruses, and certain fungi and
protozoans.
The disease may be divided into two forms, bronchial pneumonia and
lobar pneumonia.
Bronchial pneumonia is most prevalent in infants, young children and
aged adults.
It is caused by various bacteria, including Streptococcus pneumoniae.
Bronchial pneumonia involves the alveoli contiguous to the larger
bronchioles of the bronchial tree.
Lobar pneumonia is more prone to occur in younger adults. A majority
(more than 80%) of the cases of lobar pneumonia are caused by
Streptococcus pneumoniae.
Lobar pneumonia involves all of a single lobe of the lungs (although more
than one lobe may be involved), wherein the entire area of involvement
tends to become a consolidated mass, in contrast to the spongy texture of
normal lung tissue.
Streptococcus pneumoniae cells are Gram-positive, lancet-
shaped cocci (elongated cocci with a slightly pointed outer
curvature).
Usually, they are seen as pairs of cocci (diplococci), but they
may also occur singly and in short chains.
When cultured on blood agar, they are alpha hemolytic.
Individual cells are between 0.5 and 1.25 micrometers in
diameter.
They do not form spores, and they are nonmotile. Like other
streptococci, they lack catalase and ferment glucose to lactic
acid.
Unlike other streptococci, they do not display an M protein, they
hydrolyze inulin, and their cell wall composition is characteristic
both in terms of their peptidoglycan and their teichoic acid.
Gram Stain of a film of sputum from a case
of lobar pneumonia. CDC.
Streptococcus pneumoniae is a fastidious bacterium, growing best in 5%
carbon dioxide.
Nearly 20% of fresh clinical isolates require fully anaerobic conditions.

In all cases, growth requires a source of catalase (e.g. blood) to neutralize

the large amount of hydrogen peroxide produced by the bacteria. 

In complex media containing blood, at 37°C,  the bacterium has a doubling

time of 20-30 minutes.

On agar, pneumococci grow as  glistening colonies, about 1 mm in

diameter.
Two serotypes, types 3 and 37, are mucoid. Pneumococci spontaneously
undergo a genetically determined, phase variation from opaque to
transparent colonies at a rate of 1 in 105 .
The transparent colony type is adapted to colonization of the nasopharynx,
whereas the opaque variant is suited for survival in blood.

The chemical basis for the difference in colony appearance is not known,
but significant difference in surface protein expression between the two
types has been shown.
Streptococcus pneumoniae is a very fragile bacterium and
contains within itself the enzymatic ability to disrupt and to
disintegrate the cells.
The enzyme responsible is called an autolysin.
The physiological role of this autolysin is to cause the culture to
undergo a characteristic autolysis that kills the entire culture
when grown to stationary phase.
Virtually all clinical isolates of pneumococci harbor this
autolysin and undergo lysis usually beginning between 18-24
hours after initiation of growth under optimal conditions.
Autolysis is consistent with changes in colony morphology.
Colonies initially appear with a plateau-type morphology, then
start to collapse in the centres when autolysis begins.
 Streptococcus pneumoniae A
mucoid strain on blood agar
showing alpha hemolysis
(green zone surrounding
colonies). Note the zone of
inhibition around a filter paper
disc impregnated with
optochin.
Viridans streptococci are not
inhibited by optochin.

Streptococcus pneumoniae
Quellung (capsular swelling)
reaction can be used to
demonstrate the presence of
a specific capsular type of
the bacterium.
Capsule
A capsule composed of polysaccharide completely envelops
the pneumococcal cells.
During invasion the capsule is an essential determinant of
virulence.
The capsule interferes with phagocytosis by preventing
complement C3b opsonization of the bacterial cells. 90
different capsule types of pneumococci have been identified
and form the basis of antigenic serotyping of the organism.
Anti-pneumococcal vaccines are based on formulations of
various capsular (polysaccharide) antigens derived from the
highly-prevalent strains.
Pneumococci spontaneously cause disease in humans,
monkeys, rabbits, horses, mice and guinea pigs.
Nasopharyngeal colonization occurs in approximately 40% of
the population.
Pneumonia and otitis media are the most common infections,
meningitis being much more variable.
The rabbit and the mouse have been used extensively as
animal models of disease, leading to a reasonable
understanding of many of the pneumococcal determinants of
virulence.
Hydrogen peroxide
H2O2 produced by the pneumococcus causes damage to host
cells and has bactericidal effects against competing bacteria
such as Staphylococcus aureus.
Streptococcus
pneumoniae
meningitis
Streptococcus pneumoniae
Corynebacterium diphtheriae
Corynebacteria are Gram-positive, aerobic, nonmotile, rod-
shaped bacteria classified as Actinobacteria.
Corynebacteria are related phylogenetically to mycobacteria
and actinomycetes.
They do not form spores or branch as do the actinomycetes,
but they have the characteristic of forming irregular, club-
shaped or V-shaped arrangements in normal growth.
They undergo snapping movements just after cell division,
which brings them into characteristic forms resembling Chinese
letters or palisades.
Stained Corynebacterium cells. The "barred" appearance
is due to the presence of polyphosphate inclusions called
metachromatic granules. Note also the characteristic
"Chinese-letter" arrangement of cells.
Diphtheria is an upper respiratory tract illness characterized by
sore throat, low fever, and an adherent membrane (called a
pseudomembrane) on the tonsils, pharynx, and/or nasal
cavity. 
Diphtheria toxin produced by C. diphtheriae, can cause
myocarditis, polyneuritis, and other systemic toxic effects. A
milder form of diphtheria can be restricted to the skin.

Diphtheria is a contagious disease spread by direct physical

contact or breathing aerosolized secretions of infected
individuals.

Diphtheria is a serious disease, with fatality rates between 5%

and 10%. In children under 5 years and adults over 40 years,
the fatality rate may be as much as 20%. Outbreaks, although
very rare, still occur worldwide, even in developed nations.
CDC describes diphtheria as an upper respiratory tract illness
characterized by sore throat, low-grade fever, and an adherent
membrane of the tonsil(s), pharynx, and/or nose.
Diphtheria is a rapidly developing, acute, febrile infection which
involves both local and systemic pathology.
A local lesion develops in the upper respiratory tract and
involves necrotic injury to epithelial cells.
As a result of this injury, blood plasma leaks into the area and a
fibrin network forms which is interlaced with rapidly-growing C.
diphtheriae cells.
This membranous network, called a pseudomembrane, covers
over the site of the local lesion leading to respiratory distress,
even suffocation.
Three strains of Corynebacterium diphtheriae are recognized,
gravis, intermedius and mitis.
Immunity to Diphtheria
Acquired immunity to diphtheria is due primarily to toxin-neutralizing
antibody (antitoxin). Passive immunity in utero is acquired
transplacentally and can last at most 1 or 2 years after birth.

Individuals that have fully recovered from diphtheria might continue

to harbour the organisms in the throat or nose for weeks or even
months.
In the past, it was mainly through such healthy carriers that the
disease was spread, and toxigenic bacteria were maintained in the
population. Before mass immunization of children, carrier rates of C.
diphtheriae of 5% or higher were observed.

Because of the high degree of susceptibility of children, artificial

immunization at an early age is universally advocated. Toxoid is
given in 2 or 3 doses (1 month apart) for primary immunization at an
age of 3 - 4 months.
A booster injection should be given about a year later, and it is
advisable to administer several booster injections during childhood.
 Diphtheria
pseudomembrane.
Klebsiella pneumoniae
Klebsiella infections tend to occur in people with a weakened
immune system.
Many of these infections are obtained when a person is in the
hospital for some other reason.
The most common infection caused by Klebsiella bacteria
outside the hospital is pneumonia.
Klebsiella pneumonia tends to affect people with underlying
diseases, such as alcoholism, diabetes and chronic lung
disease.
Classically, Klebsiella pneumonia causes a severe, rapid-onset
illness that often causes areas of destruction in the lung.
Klebsiella pneumoniae is a Gram-negative, non-motile,
encapsulated, lactose fermenting, facultative anaerobic, rod
shaped bacterium, sticky mucoid colonies found in the normal
flora of the mouth, skin, and intestines.
New antibiotic resistant strains of K. pneumoniae are appearing,
and it is increasingly found as a nosocomial infection.
Klebsiella pneumoniae infections are common in hospitals where
they cause pneumonia (characterized by emission of bloody
sputum) and urinary tract infections in catheterized patients.
Klebsiella pneumoniae
Klebsiella pneumoniae
Gram-negative bacilli, Klebsiella pneumoniae, isolated
from a lung abscess in a patient with pneumonia.
Klebsiella bacteria are usually resistant to many antibiotics,
including penicillin.
Doctors will sometimes treat a patient with two different
antibiotics in an effort to stop a K.pneumoniae infection.
In order to determine which antibiotic is the best, a culture of
the infected area is taken with a sterile swab.
Often, a catheter tip of a piece of breathing tube is submitted
for culture.
Sputum and urine are also samples that can be cultured.
 Mycobacterium tuberculosis
Galloping Consumption, White Death, White Plague

Tuberculosis complex organisms are:

Obligate aerobes growing most successfully in tissues with a high
oxygen content, such as the lungs.

Facultative intracellular pathogens usually infecting mononuclear

phagocytes (e.g. macrophages).

Slow-growing with a generation time of 12 to 18 hours (c.f. 20-30

minutes for Escherichia coli).

Hydrophobic with a high lipid content in the cell wall.

Because the cells are hydrophobic and tend to clump together, they
are impermeable to the usual stains, e.g. Gram’s Stain.
Known as "acid-fast bacilli" because of their lipid-rich cell
walls, which are relatively impermeable to various basic dyes
unless the dyes are combined with phenol.
Once stained, the cells resist decolorization with acidified
organic solvents and are therefore called "acid-fast".
(Other bacteria which also contain mycolic acids, such as
Nocardia, can also exhibit this feature.)
Ziehl-Neelsen (ZN Stain) acid-fast staining procedure.
Symptoms of tuberculosis include:

Fever, Night-time sweating, Loss of weight, Persistent cough,

Constant tiredness, Loss of appetite.
Tuberculosis kills 3,000,000 people in the world every year,
more than AIDS, malaria, and other tropical disease combined.
One third of the world's population is infected with tuberculosis.
Tuberculosis is the leading infectious disease cause of death and
represents more than a quarter of the world's preventable
deaths.
Transmission of TB occurs primarily by the aerosol route but can
also occur through the gastrointestinal tract.
Coughing by people with active TB produces droplet nuclei
containing infectious organisms which can remain suspended in
the air for several hours.
Infection occurs if inhalation of these droplets results in the
organism reaching the alveoli of the lungs.
In the lung, the organism is taken up by alveolar macrophages
and carried to lymph nodes, from where it may spread to
multiple organs.
Two to eight weeks after infection, cell mediated immunity (CMI)
and hypersensitivity develop leading to the characteristic
reaction to the tuberculin test.
BCG (Bacille Calmette Guerin)
Inflammatory immune responses eventually result in lung
damage.
TB is currently treated by means of combination therapy, using
cocktails of 3-4 drugs with different properties:
Antibacterial activity: e.g. isoniazid, rifampin, streptomycin
Inhibiting the development of resistance: e.g. isoniazid,
rifampin, ethambutol
Mycobacterium tuberculosis
ZN Stain
Culture of TB on Lowenstein Jensen Media
Bordetella pertussis
Whooping Cough

Whooping cough
(pertussis) is caused
by the bacterium
Bordetella pertussis,
B. pertussis  is a very
small Gram-negative
aerobic coccobacillus
that appears singly or
in pairs.
 The disease pertussis has two stages.
The first stage, colonization, is an upper respiratory disease with
fever, malaise and coughing, which increases in intensity over
about a 10-day period.
During this stage the organism can be recovered in large
numbers from pharyngeal cultures, and the severity and duration
of the disease can be reduced by antimicrobial treatment.
The second or toxaemic stage of pertussis follows relatively non
specific symptoms of the colonizaton stage.
It begins gradually with prolonged and paroxysmal coughing that
often ends in a characteristic inspiratory gasp (whoop).
B. pertussis produces a variety of substances with toxic activity in
the class of exotoxins and endotoxins.
Antibiotic therapy may ameliorate symptoms and minimise
transmission of the organism to susceptible contacts, but only
if commenced within 21 days of onset of symptoms.

Treatment includes:
Azithromycin 500 mg (child ≥ 6 months: 10 mg/kg up to
500 mg) orally on day 1, then 250 mg (child ≥ 6 months:
5 mg/kg up to 250 mg) orally for a further 4 days, or child
< 6 months: 10 mg/kg orally, daily, for 5 days.
OR
Clarithromycin 500 mg (child > 1 month: 7.5 mg/kg up to
500 mg) orally, 12-hourly, for 7 days.
OR
Erythromycin 250 mg (child > 1 month: 10 mg/kg up to 250
mg) orally, 6-hourly, for 7 days or erythromycin (ethyl succinate
formulation) 400 mg (child > 1 month: 10 mg/kg up to 400 mg)
orally, 6-hourly, for 7 days.
Colonies of Bordetella pertussis
Pertussis Coccobacillus
Gram
 Mycoplasma pneumoniae
Mycoplasma pneumoniae is a common cause of community-
acquired pneumonia, and, usually, the disease has a
prolonged, gradual onset.
M pneumoniae was first isolated in cattle with pleuropneumonia
in 1898.
The responsible organism, M pneumoniae, is a pleomorphic
organism that, unlike bacteria, lacks a cell wall, and unlike
viruses do not need a host cell for replication. The prolonged
paroxysmal cough seen in this disease is thought to be due to
the inhibition of ciliary movement. The organism has a
remarkable gliding motility and specialized filamentous tips end
that allows it to burrow between cilia within the respiratory
epithelium, eventually causing sloughing of the respiratory
epithelial cells.
In almost all patients, the pneumonia resolves without any
serious complications.
M. pneumoniae can cause severe pneumonia in children and
has recently been associated with acute chest syndrome in
patients with sickle cell anaemia. 
Mycoplasmal pneumonia is a disease of gradual and insidious onset of several
days to weeks. The patient's history may include the following:

Fever
Malaise
Persistent, slowly worsening dry cough; absence of cough makes the diagnosis of
M pneumoniae unlikely
Headache
Chills, not rigors
Scratchy sore throat
Sore chest and tracheal tenderness (result of the protracted cough)
Pleuritic chest pain (rare)

Sputum Gram stains and cultures usually are not helpful, since M
pneumoniae lacks a cell wall and cannot be stained. 
 Coxiella burnetti
Q fever is a zoonotic disease caused by Coxiella burnetii, a
species of bacteria that is distributed globally. 
Cattle, sheep, and goats are the primary reservoirs of C. burnetii.
Infection has been noted in a wide variety of other animals,
including other species of livestock and in domesticated pets.
Coxiella burnetii does not usually cause clinical disease in these
animals, although abortion in goats and sheep has been linked to
C. burnetii infection.
Organisms are excreted in milk, urine, and feces of infected
animals. Most importantly, during birthing the organisms are shed
in high numbers within the amniotic fluids and the placenta.
A zoonotic disease is an infection which can be
transmitted from animals to humans.
The organisms are resistant to heat, drying, and many common
disinfectants. 
These features enable the bacteria to survive for long periods
in the environment. 
Infection of humans usually occurs by inhalation of these
organisms from air that contains airborne barnyard dust
contaminated by dried placental material, birth fluids, and
excreta of infected herd animals. 
Humans are often very susceptible to the disease, and very few
organisms may be required to cause infection.
Other modes of transmission to humans, including tick bites
and human to human transmission, are rare.
Chronic Q fever, characterized by infection that persists for
more than 6 months is uncommon but is a much more serious
disease.
Patients who have had acute Q fever may develop the chronic
form as soon as 1 year or as long as 20 years after initial
infection.
A serious complication of chronic Q fever is endocarditis,
generally involving the aortic heart valves, less commonly the
mitral valve.
1%-2% of people with acute Q fever die of the disease.
Confirming a diagnosis of Q fever requires serologic testing to
detect the presence of antibodies to Coxiella burnetii antigens.
In most laboratories, the indirect immunofluorescence assay
(IFA) is the most dependable and widely used method.
Coxiella burnetii may also be identified in infected tissues by
using immunohistochemical staining and DNA detection
methods.
Doxycycline is the treatment of choice for acute Q fever.
Antibiotic treatment is most effective when initiated within
the first 3 days of illness.
Coxiella burnetii is a highly infectious agent that is rather
resistant to heat and drying. It can become airborne and
inhaled by humans. A single C. burnetii organism may
cause disease in a susceptible person.
 Chlamydia psittaci
also referred to as Psittacosis, Parrot Fever or
chlamydiosis.
The word Psittacosis comes from the Greek word Psittakos,
meaning parrot.
Chlamydia are gram negative, spherical, (0.4-0.6 micron
diameter), intracellular parasites
In birds, C. psittaci may manifest itself as an upper
respiratory infection with nasal, and or ocular discharge,
diarrhea, or a combination of all three. In some cases, birds
may be infected but show no signs. These cases are of
concern because these birds may become carriers and
shed the organism.
*C. psittaci is related to Chlamydia trachomatis, the most
common human STD, and Chlamydia pneumonia, a cause of
human pneumonia.
Chlamydia pneumonia is also being investigated as possibly
being associated with cardiovascular disease in humans.
Transmission of this organism from one host to another is
primarily through the air.
The bacteria is shed from an infected bird in the nasal and or
ocular secretions, fecal material, and feather dust.
The organism remains remarkably stable outside the host body
and dries as a dusty substance.
This dust or aerosol contaminates the air that is then inhaled by
another possible host.
The disease has a greater chance of spreading in
overcrowded conditions, stale air environments, nest-
boxes, and brooders.
Pet shops, bird marts, and quarantine stations are also
high risk areas.

Transmission of the Chlamydial organism from birds to

humans has been confirmed in a number of cases.
Although psittacosis infection in humans is rare it is
potentially dangerous for persons who are sick, elderly,
immunosuppressed (e.g., HIV patients) or pregnant.
Most treatments involve the use of tetracycline and its
derivatives such as Vibramycin, Doxycycline,
Oxytetracycline.
The antibiotic can be given by intravenous or
intramuscular injections.
Antibiotics can also be given orally or mixed with
palatable food.
Treatment periods generally last about 45 days
varying slightly depending on the treatment.
Calcium should be withheld because tetracycline binds
to calcium. Citric acid in the bird's drinking water can
increase the levels of antibiotics in the blood.
Chlamydia psittaci
The End