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Year Level 6 [Module 5: Basic Pathologies 2]
BACTERIAL INFECTIONS (3)
Ernesto V. Datu, MD
September 11, 2009
OUTLINE
I. Chancroid (soft chancre)
II. Granuloma Inguinale
III. Mycobacteria
A. Tuberculosis
B. Leprosy
IV. Spirochetes
A. Syphilis
B. Lyme’s Disease
V. Anaerobic Bacteria
VI. Obligate Intracellular Infections
A. Chlamydial infections
B. Rickettsial infections
I.
II.
CHANCROID (SOFT CHANCRE)
A. Microbiology & Epidemiology

Hemophilus ducreyi

Fastidious Gram-negative organism

Most common cause of genital ulcers in Africa and
Southeast Asia: is a co-factor to HIV

Not present here in the Philippines; common in
Thailand (even the monks in Thailand have this )
B. Transmission

This disease is sexually transmitted – therefore
sexual history is important to determine
C. Presentation

Lesion comes out from the skin and not in the
urethra

These lesions are soft and are very painful

Lymph nodes are also enlarged due to pus – this is
known also as “bubose”

A chancre, like syphilis, but it is soft

Similar to Yersinia pestis where lymph nodes are
soft because of pus inside
D. Treatment

Treatment involves draining the pus from the
lymph node
GRANULOMA INGUINALE
A. Microbiology & Epidemiology

Calymmatobacterium donovani

More common name is Klebsiella granulomatis

Also known as Donovanosis

Gram-negative encapsulated coccobacillus
B. Transmission

Sexually transmitted
C. Presentation

Formation of many genital ulcers – these are
painless

Fibrosis of lymph nodes – so inguinal area seems
contracted

Can develop elephantiasis of the scrotum and legs

Produces scarring

In extreme cases, blood vessels are fibrosed and
skin sloughs off, exposing inner structures
Figure 1. Ulcers in the
penis are painless. In
comparison to syphilis,
there are more lesions in
granuloma inguinale.
(A)
(B)
Figure 2. (A) Elephantiasis of the leg or scrotum can
also occur. (B) The skin of the scrotum can also
necrose, which can lead to exposure of the balls.
III. MYCOBACTERIA
A. Tuberculosis

Mycobacteria are neither gram positive or negative
due to the lining that has mycolic acid

So classification is done by acid fast staining
o In acid fastness, the background is blue but
there are presences of red strip organisms.
o These red strip organisms confirm the
presence of acid fast organisms.

Slender aerobic bacillus
o With straight or branching chains
o With Mycolic acid

Waxy

Acid fastness – because of mycolic acid, it
is not subject to the usual gram staining
Figure 3. Comparison between walls of GPB, GNB & AF organisms.
Team 3 | Annie. Charisse. Emil. Ginger. Kevz. Marian. Pam. Pau. Pier. Tadz
Page1of 8
BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009

Comparison between walls of GBP, GNB & AF organisms:

Gram (+) has peptidoglycan.

Gram (-) has peptidoglycan plus an LPS.

Acid-fast organisms have an arabinogalactan and
mycolic acid. The arabinogalacta is made up of malose.
Microbiology & Epidemiology

It is important that infection with M. tuberculosis be
differentiated from disease.

If you’re infected with M .tuberculosis, does it occur as
tuberculosis right away? No. Infection is different from
disease! Being infected, it doesn’t follow that you
develop the disease. This always depends on the host’s
immune system. Just remember, almost all of us
Filipinos have been exposed to M. tuberculosis but not
all of us have the disease.

In most people primary tuberculosis is asymptomatic,
although it may cause fever and pleural effusion.
Generally, the only evidence of infection, if any remains,
is a tiny, fibrocalcific nodule at the site of the infection.
Viable organisms may remain dormant in such lesions
for decades. If immune defenses are lowered, the
infection may reactivate to produce communicable and
potentially life-threatening disease.

Rate of disease depends on the immunity of the person.
o Asymptomatic if immune system is good
o But some reactivate especially if the immune
system is challenged by exposure to the endemic
TB (since TB is endemic here in the Philippines,
reactivation is common)
o
Steps for tuberculin test:
1. Administer PPD intradermally using
an intradermal syringe (in between
skin cells). Then measure the
induration. If > 0.5cm, then he/she is
positive.
2. In the Phils, since we are endemic,
positive is 10 cm. In the US, positive
is 50 cm.
Delayed-Type Hypersensitivity

A positive tuberculin test result signifies T cellmediated immunity to mycobacterial antigens

This means that this test is dependent on
intact T cells

However, it does not differentiate between
infection and disease. We can get false
positive and false negative results.
False negative:

In cases of patients having low CD4 counts (ex.AIDS
patient), we cannot expect a good T cell response. The
result may give a negative result even if the patient is
really positive for the infection.
False positive:

Associated with BCG (Bacillus Calmette-Guerin)
 Effective in stimulating delayed type hypersensitivity
Transmission: mainly by airborne or droplet
Pathophysiology

In TB, the cell mediated immune response is activated
o 2 types of cell mediated immune response
(TH1 and TH2):
1. In TB, the delayed or cytotoxic cell
mediated hypersensitivity (TH1) is more
important.
2. Activation of cytotoxic T cells is a “double
edge sword” – it destroys t`e antigen but
it can also destroy host cells. (ex. In
Hepatic TB: cytotoxic T cells kill the virus
but also the hepatocytes.) The delayed
type hypersensitivity reaction (DTH) can
itself cause tissue destruction

Tuberculin Test
o Tuberculin is a glycerol extract of the tubercle
bacillus
o Mantoux Skin Test
o Tuberculin Sensitivity Test

PPD: Purified protein derivative

Positive: visible palpable induration in 49-72
hours

Remember that we measure the
induration by palpation. We do not
measure the erythema.

Induration: palpable raised hardened
area
Team 3
Figure 4. With primary infections (unsensitized individuals), the bacillus
is recognized by the macrophage, its primary target cell. The bacillus
is internalized but it does not fuse with the lyzosomes to become
phagolyzosomes. The macrophage thus acts as a carrier of the bacilli
within itself, and it can lead to seeding of multiple sites. This can
develop into bacteremia.
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BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009




TH1 produces IFN-γ, which will activate macrophages. This
will thus trigger phagosome fusion with lysosome for
digestion of the bacilli.
As a consequence of this activation, there is a release of
chemokines.
With chemokine and TNF release  recruitment of more
monocytes  formation of an epitheliod granuloma
Granuloma formation may harbor the infection and with
immunosuppression, may cause reactivation.
Figure 5. The response is initiated by mycobacterial antigens that enter
draining lymph nodes & are displayed to T-cells. M. tuberculosis
makes several molecules that are ligands for TLR2 and stimulation of
TLR2 by these ligands promotes production of IL-12 by dendritic
cells.
Figure 6. IFN-γ is the critical mediator that enables macrophages to
contain the M. tuberculosis infection. Inducible nitric oxide synthaseTNF promotes recruitment of more monocytes.
Granuloma (Figure 7):

Made up of epitheloid cells which are activated macrophages

TB infection may be contained in the granuloma (caseating
granulomas)
o Since TB resides in the macrophages, this enables TB to
hide in the granuloma which is an aggregation of
activated macrophages.
o It stays in the granuloma free from detection and this
causes the infection to be in a quiescent stage.
o If the immunity of the host becomes compromised,
reactivation may occur.
Summary of the figures:

Macrophage is primary target cell of infection

Initial infection: bacilli is nternalized but phagosome does
not fuse with lysosome.

Macrophage presents to undifferentiated Tcell via IL-12,
which becomes TH1.
Team 3
Figure 8. Caseous Necrosis. Pink amorphous deposits. Presence of
Langhans cells (but even without this, it can still be characteristic of
TB. Presence of epithelioid cells. Epithelioid cells are the hallmark of
TB and they are made up of modified macrophages.
In Unsensitized individuals

It takes 3 weeks after initial infection for the normal
immune system to respond

Within 1-3 weeks, the organism can enter the
circulation but the immune system is not able to detect
it yet.

Again, eventually there is macrophage activation
o TH1 cells:

Presented with class II major
histocompatibility proteins

TB is intracellular

IFN-γ production leads to:

Phagolysosome formation
Granuloma and caseous necrosis
Epitheliod cells
Secondary tuberculosis

Reactivation vs. re-infection
o In endemic areas, like the Philippines, the initial
infection may be re-activated (due to quiescent
stay of the bacillus within granulomas) when the
host immunity is compromised.
o In non-endemic areas, a person can be infected
again. Re-infection is being infected again, different
from re-activation of the same initial infection.
Presentation

Low grade fever and night sweats – classic symptoms
(triggered by TNF and IL-1)

Sputum
o Mucoid, purulent
o Hemoptysis
Page3of 8
BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009


TB is not a pyogenic organism
o Neutrophils are not needed to remove the disease.
Morphology-Lungs
o Gohn complex

Also known as the primary complex

Initial lesion of TB

Subpleural location

Lower part of the upper lobe

Upper part of the lower lobe

Sensitization

1 to 1.5 cm with caseous necrosis

Perihilar lymph node involvement

Within the first 1-3 weeks, the organism
is not yet detected by the macrophages
so they go to the lymph nodes first.

With sensitization, caseation sets in

Necrosis is also present: casseous
necrosis
cheese-like
always subpleural location
can also be found in perihilar LN

Fibrosis

Calcification

When lesion in this areas is prolonged
(chronic); calcification may occur
Calcifications are determined by
using staining. These calcifications
take up the blue stain very well.

Calcifications are also determined by xray  Ranke Complex
Figure 9. Presence of
subpleural effusion. Caseous
necrosis (kesong puti;
cheese-like).
Figure 10. Microscopically: Calcification is the extremely blue
lesion, which is an aggregation of hemotoxylin. It is covered by
fibrin deposition. Granuloma—pink morphous material.
Team 3
Different Presentations:
1. Primary Tuberculosis

Usually asymptomatic

Possible reactivation

Important: function of Cell Mediated Immune
Response
2.
Secondary Tuberculosis

Involvement of Apical regions of the lungs
o 1-2 cm
o apical portion of lungs, since there is high
oxygen there, and the organism loves oxygen
(an aerobic bacteria)
3.
Progressive Pulmonary Tuberculosis

Apical lesion enlarges

Hemoptysis
o Evacuated caseous material leaves the lungs
(grossly, you see clear holes that were
previously occupied by caseation)
o The caseous material actually leaves the lungs
and is expelled through the respiratory tract
as blood tinged sputum (hemoptysis)
o “Pag-ubo ng dugo” is a very classic
manifestation of TB in our country
o Gross:

Increase in size of lesions

Lesions are spreading in other areas
because it is already systemic

Caseous necrotic material can escape the
bronchoalveolar lining. This can lead to
hemoptysis.
4.
Miliary Pulmonary Tuberculosis

This occurs when casseation involves the
lymphatics (perihilar LNs) and goes to the right side
of the heart and pulmonary arteries.

Review the flow of blood in the heart and lungs
o If there is TB in the pulmonary arteries, blood
then goes back

Miliary
o Described as military because it is similar to
the appearance of miliary seeds (bird feed)
o Small areas of TB that are separated from
each other (small whitish dots)
o Here, the pulmonary artery is affected
Figure 11. Tuberculosis exhibits the following: Pleural effusion;
Tuberculous emphysema; Obliterative fibrous pleuritis;
Endobronchial, endotracheal & laryngeal tuberculosis.
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BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009
5.
6.
7.
Team 3
Systemic Tuberculosis

Miliary seeding in the lungs may spread to other
organs

Aside from the lungs, the spleen may also present
miliary seeding

Complications of Systemic Tuberculosis:
a) Lymphadenitis

Cervical lymph node involvement
o Scrofula – big mass in the neck
o Rare
b) Intestinal tuberculosis

Secondary to miliary seeding

Copious sputum may lead to infection of
intestines. Swallowing of sputum may
trigger infection in the intestines.
c) Hydrocephalus

Brain involvement

Systemic TB can cause hydrocephalus

Common in the Philippines

This is an irreversible condition. In order
to relieve this, put a shunt in the head
and transfer the fluid to the peritoneum.
d) General rule in systemic TB

If the caseous area is small, lesion is only
secondary to miliary seeding

If the caseous area is big, that is consider
as the primary lesion (commonly seen in
the brain)
Isolated Organ Tuberculosis

TB may also be seen, not with miliary presentation
(small seed-like dots) but as large caseation)

Seen in :
o Meninges – TB meningitis
o Kidneys – isolated TB is unique in the kidney
o Adrenals
o Bone
o Vertebra – Pott’s disease
Mycobacterium Avium-Intracellulare Complex (MAC)

Immunosuppressed (HIV patients)
o Normal individuals: manifest presentation like
primary TB. However, no casseation is present
and it cannot mount a hypersensitivity
reaction.
o Absence of caseation is a good sign. However,
it may become rampant because there is no
immune reaction.

Abundant acid-fast bacilli within macrophages
o Lymph nodes, liver and spleen
Figure 12. Macrophages are filled with acid fast bacilli. This
shows that the macrophages are unable to kill the
intracellular organisms. Unlike in TB, there is no caseation
present here. HIV with TB patients can also show the same
histological preparation.
B.
Leprosy
Microbiology

Mycobacterium leprae

Acid fast, obligate intracellular organism (cousin of
Mycobacerium Tuberculosis)

Immunization for BCG is also preventive for leprare

Missing genes from original mycobacteria from original
mycobacterium-> probably reason why they prefer
lower temperature.

32 to 34 o C – therefore it cannot survive in our body
temperature except from some areas.

Vector is the Armadillo (animal that has nine bands)
o Common in the US
o So if you see one, do not touch it!

Lepromin Test: test of M. leprae antigen
Presentation

Hansen’s disease

Respiratory infection

Cool tissues of the skin and extremities
2 Types of Leprosy—depending on the immunity of person
1. Tuberculoid (good immunity)

Normal TH1 response
o IL-12

Presentation:
o Skin involvement is asymmetric
o Nerve involvement:
o A consequence of granuloma formation
o Skin anesthesia and skin ulcers

Presence of whitish lesions that if
pricked, the person having this will
not feel anything.
o Facial nerve involvement also
o “Die with it rather than of it”

Grossly:
o Skin shows whitish lesions: tuberculoid
deposit
o If you pin prick, will exhibit bleeding
o Be careful because it is infectious
Page5of 8
BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009

2.
Lepromatous (deficit immunity)

IL-12 deficient
o Deficient macrophage activation
o Anergic leprosy

This is never mild

Nerve involvement is more severe
o Due to organism not inflammation

Microscopically, you see Lepra cells (light area)
o These cells can spread, does not follow the 3234 Temp rule

Presentation:
o Shows symmetric skin lesions: thickening,
nodule formation
o Spleen, liver and testicular involvement
o In spleen, you see a mass filled with myco
bacilli)
o Skin thickens and forms nodules (layering
fascia)
o Also found in the arms
o The testes have lower temperature and can be
a site of lepromatous leprosy

Organism destroys sensory nerves
o Because the sensory nerves are destroyed and
not the motor, the person become insensitive
to feeling.
o Hands are feet are the usual targets. Because
they cannot feel anything in their hands and
feet, these two are often full of wounds.
o Constant trauma leads to disfigurement.

Also presents epitheloid cells and giants cells but
without casseation
IV. SPIROCHETES
A. Syphilis

Treponema pallidum

Identification: Silver stains, dark field microscopy,
IF, ELSIA
o Use modified stains

Penicillin-susceptible

This is a sexually-transmitted disease
Stages
a) Primary Syphilis: First weeks

Lesions are not painful

Single firm, non tender raised lesion

A hard chancre

Heals in 3- 6 weeks

Commonly seen in the sex organs but also seen in
the lip, tongue and anus
b)
Team 3
Secondary Syphilis: 2 to 10 weeks later

Usually heals by itself

In 75% of untreated cases, it comes back with a
different presentation
o Skin and mucocutaneous tissue
o Palms and soles – indicative for syphilis

Maculopapular

Scaly

Pustular
o
o
o
o
o
c)
If these three are seen, scrape some of
these areas and test for the presence of
T. pallidum. This is infective.
Condylomata lata

Wart like lesions

Heals by itself

If you cut sections of it, you will see
spirochetes inside
Erosions of the skin and mucous membranes
Lymphadenopathies
It may look like measles
Lesions can also be found in the mouth and
anus
Tertiary Syphilis

In 1/3 of untreated patients, it comes back again

3 – 5 years

Complications:
i. Cardiovascular Syphilis – may trigger heart
diseases

May develop Syphilitic aortitis
characterized by aortic aneurysm

Aortic aneursym

Aorta gets its own blood from the
vasa vasorum which can be seen at
the outer part of the aorta.

Syphilis attacks the vasa vasorum
leading to necrosis or aneurysm of
the aorta.

If this is filled with blood, it may
become a dissecting aneurysm and
is life-threatening.
ii.
Neurosyphilis

Psychiatric conditions: changes in mood

Meningovascular

Tabes dorsalis

General paresis
iii.
Benign Tertiary Syphilis

Best one to have

Presents Gumma formation: a form of
granuloma but without the characteristic
casseation

Involvement also of the bone, skin and
mucous membranes
Special Characteristics:
1. Endarteritis

Outer third of the blood vessel loses its blood
supply

Blood vessels are inflamed

2 types:
o Proliferative: perivascular inflammation leads
to onion skinning
o Obliterative: thinning of the blood vessels
until it is completely obliterated
Page6of 8
BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009
**Note: the lecture ended here. Dr. Datu instructed us to read on
the following on our own.
Figure 14. Notice the vasa vasorum blood vessel involvement.
2.
3.
Hepar lobatum

Not brought about by the primary event

Characteristic of tertiary syphilis

Not form of cirrhosis but looks like it

Exhbits normal hepatic cells in islands

Mononuclear infiltrates inside these islands
Gumma formation

Presence of fibrosis of blood vessels
Congenital Syphilis

In Primary and Secondary Syphilis, there is still presence
of circulating organism. In tertiary, the organism is
absent

Early Manifestations (infantile)
o “snuffles” – the infant seem to have colds always
o With bullae as early manifestation: large vesicles in
the palms, hands, face, ear

Late Manifestations (tradive)
o Rash

Rash of congenital syphilis is more severe
than that of adult secondary syphilis.

It is a bullous eruption of the palms and soles
of the feet associated with epidermal
sloughing
o Saddle nose deformity

The vomer bone is affected that is why nose is
deformed
o Interstitial keratitis

Use a slit lamp to visualize

Presence of opacity
o
Hutchinson teeth

Knotch teeth and molars are flat
o Hutchinson’s Triad )Eight-nerve deafness)

Eighth-nerve deafness and optic nerve
atrophy develop secondary to
meningovascular syphilis.
o Syphilitic Osteochondritis and Periostitis

Found in the tibia

Usually occurs early but may also develop late

Overgrowth of bone
Serological Tests

Nontreponemal
o Antibodies to cardiolipin

Phospholipid

RPR

VDRL
o 4-6 weeks
o 15%- biologic false positives

Treponemal antibody tests
o FTA-Abs
o MHATP-TPHA
o 4-6 weeks
o 2% false positive
Relapsing fever

Borrelia recurrentis

Ornithodorus ticks
o Soft-bodied

Pediculus humanus
Figure 16. Ornithodorous tick hosts.
Figure 17. Relapsing fever in spirochete infection.
Figure 15. Hutchinson teeth.
Team 3
Page7of 8
BACTERIAL INFECTIONS (3)
Year Level 6 [Module 5: Basic Pathologies 2]|September 11, 2009
B.
Lyme’s Disease

Borrelia burgdorferi
o Has a a single promoter sequence and
multiple coding sequences for an antigenic
surface protein, VlsE, each of which can
shuttle into position next to the promoter and
be expressed

Ixodes (Deer ticks)
Borrelia burgdorferi

Antigenic variation
o Antigenic surface protein-VlsE

CD4+ helper T cells and B cells
Figure 18. Clinical stages of Lyme disease.
V.
ANAEROBIC BACTERIA

Clostridial Infections
o Gram-positive
o Sporeformers

Abscesses Caused by Anaerobes
o Commensal bacteria from adjacent sites
(oropharynx, intestine, and female genital tract)
are the usual cause of abscesses, so the species
found in the abscess reflect the normal flora.
A.
B.
Team 3
Clostridium perfringens

Cellulitis

Myonecrosis
o Surgical wounds
o Illegal abortions

Collagenase and hyaluronidase

14 toxins
o α -Toxin

Phospholipase C

Sphingomyelinase

Diarrhea
Clostridum tetani

Gram-positive bacilli

Tetanus
o Tetanospasmin

Block the release of γ-aminobutyric acid

Spastic paralysis

Lockjaw

risus sardonicus
C.
D.
Clostridium botulinum

Botulism
o Paralysis of respiratory and skeletal muscles
o Fragment A cleaves synaptobrevin
o Acetylcholine
o Botox
Clostridium difficile

Toxin A  Enterotoxin

Toxin B  Cytokine and cytopathic

Pseudomembranous colitis
VI. OBLIGATE INTRACELLULAR INFECTIONS
A. Chlamydial infections

Chlamydia trachomatis

Urogenital infection and inclusion conjunctivitis
o Serotypes D to K

Lymphogranuloma venerum
o Serotypes L1, L2 and L3

Chronic ulcerative disease
o Papule
o Lymph node
o Fibrosis and strictures
o Lymphatic obstruction

Chlamydial Infections
o Elementary body (EB)

Infectious form---sporelike structure

Receptor mediated endocytosis

Phagolysosome fusion inhibition
o Reticulate body (RB)

Metabolically active form
o Serotypes A,B and C
o Trachoma
o Serotype D to K

NGU

Urealplasma urealyticum

Mycoplasma hominis

Trichomonas vaginalis
B.
Rickettsial infections

Vector borne

Obligate intracellular parasite

Gram-negative rod shaped bacteria

Typhus group—R. prowazekii (Human Louse)
o Cytolysis

Spotted fever group—R. rickettsii (Tick)
o Actin mobilization

Scrub typhus group—R. tsutsugamushi
o Chigger

Ehrlichiosis
o Ricketssiales
o Neutrophils and Macrophages

Cytoplasmic inclusions

Morulae

Eschar , Rash

Endothelial cell damage (in lungs and brain)

The severe manifestations of rickettsial infection
are primarily due to vascular leakage secondary to
endothelial cell damage. Rickettsiae do not
produce significant toxins.
Page8of 8