General Pathology of

Infectious Diseases

FOR PC2 STUDENTS

BY HABTE.S (MD, Pathologist, Ass.pro.)
AMU, School of Medicine, Pathology Department
2013 EC

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Out lines
• Introduction.
• Classes of human pathogens.
• Special techniques for diagnosing Infectious agents.
• Transmission and dissemination of microbes.
• Patterns of tissue reaction in infections.
• Tuberculosis.
• Syphilis.

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 Introduction
• Infectious agents belong to a wide range of classes
and vary greatly in size,

• Ranging from prion protein aggregates of under 20

nm to tapeworms 10 meters in length.

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 Classes of Human Pathogens

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 Prions
• Prions are composed of abnormal forms of a host protein termed
prion protein (PrP).
• PrP is found normally in neurons.
• Diseases occur when the PrP undergoes a conformational change
that confers resistance to proteases.
• The protease-resistant PrP promotes conversion of the normal
protease sensitive PrP to the abnormal form,
• Explaining the transmissable nature of these diseases.
• CJD can be transmitted from person to person iatrogenically, by
surgery, organ transplantation, or blood transfusion.
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 α-Helical PrPc may spontaneously shift
to the β-sheet PrPsc conformation

PrPsc (sc for scrapie)

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 Viruses

• Viruses are obligate intracellular parasites that depend on the host cell’s
metabolic machinery for their replication.

• They consist of a nucleic acid genome surrounded by a protein coat

(called a capsid) that is sometimes encased in a lipid membrane.

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Selected Human Viral Diseases and Their Pathogens

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 Bacteria

• Bacteria are prokaryotes,

• Meaning that they have a cell membrane but lack membrane-bound
nuclei and other membrane-enclosed organelles.
• Most bacteria are bounded by a cell wall consisting of peptidoglycan,
• A polymer of long sugar chains linked by peptide bridges
surrounding the cell membrane.
• There are two common forms of cell wall structure:
A thick wall that retains crystal-violet stain (gram-positive bacteria),
and
A thin cell wall surrounded by an outer membrane (gram-negative
bacteria).
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• Bacteria are classified by:
Gram staining (positive or negative),
Shape (spherical, called cocci, or rod-shaped, called bacilli) , and
Their requirement for oxygen (aerobic or anaerobic).
• Motile bacteria have flagella, long helical filaments extending from the
cell surface that rotate and move the bacteria.
• Some bacteria possess pili, another kind of surface projection that can
attach bacteria to host cells or extracellular matrix.

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• Bacteria synthesize their own DNA, RNA, and proteins,
• But they depend on the host for favourable growth conditions.

• Many bacteria remain extracellular when they grow in the host,

• While others can survive and replicate both outside and inside of host
cells (facultative intracellular bacteria such as mycobacteria), and

• Some grow only inside host cells (obligate intracellular bacteria, such as
rickettsia).

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Gram positive vs gram negative

Molecules on the surface of gram-negative and gram-positive bacteria involved in the pathogenesis of
infection.

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Selected Human Bacterial Diseases and Their Pathogens

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Cont.…

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 Fungi

• Fungi are eukaryotes with thick cell walls composed of complex

carbohydrates,
• Such as beta-glucans, chitin, and mannosylated glycoproteins.
• Calcofluor-white, a fluorescent stain that binds chitin, provides a useful
way to identify fungi in patient specimens.
• Assays for beta-glucans in blood are used to diagnose disseminated fungal
infections.

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• Fungi can grow either as rounded yeast cells or as slender,
filamentous.
• An important distinguishing characteristic of hyphae is:
• Being septated (with cell walls separating individual cells) or
aseptated.

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• Some of the most important pathogenic fungi exhibit thermal
dimorphism; that is,
• They grow as hyphal forms at room temperature but as yeast forms at
body temperature.
• Fungi may produce sexual spores or, more commonly, asexual spores
called conidia.
• The latter are produced on specialized structures or fruiting bodies
arising along the hyphal filament.

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 Fungi may cause superficial or deep infections:
Superficial infections
• Involve the skin, hair, and nails.
• Fungal species that cause superficial infections are called
dermatophytes.
• Infection of the skin is called tinea; thus,
• Tinea pedis is “athlete’s foot” and tinea capitis is scalp ringworm.
• Certain fungi invade the subcutaneous tissue, causing abscesses or
granulomas.
• Chronic infections, often in the foot, are called mycetomas.

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.Deep fungal infections:

• Can spread systemically and invade tissues,

• Destroying vital organs in immunocompromised hosts,

• Usually resolve or remain latent in otherwise normal hosts.

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• Fungi are divided into endemic and opportunistic species.
 Endemic fungi:
• Are invasive species that are usually limited to particular
geographic regions.
• E.g., Coccidioides in the southwestern United States,
Histoplasma in the Ohio River Valley).

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Cont…
Opportunistic fungi
• E.g., Candida, Aspergillus, Mucor, Cryptococcus,
• Do not cause severe disease in healthy individuals.
• In immunodeficient individuals, Opportunistic fungi give rise to
lifethreatening invasive infections characterized by:
Vascular occlusion, Hemorrhage, and tissue necrosis, with little or
no inflammatory response.
• Patients with AIDS are very susceptible to infection with the
opportunistic fungus Pneumocystis jiroveci.

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 Protozoa

• Protozoa are single-celled eukaryotes.

• Are major causes of disease and death in developing countries.
• Protozoa can replicate intracellularly - like Plasmodium in red cells,
Leishmania in macrophages;
• Extracellularly in the urogenital system, intestine, or blood.
• Trichomonas vaginalis often colonize the vagina and male urethra.

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Pathogenic intestinal protozoans:
• Entamoeba histolytica and Giardia lamblia,
• Are ingested as non-motile cysts in contaminated food or water, and
• Become motile trophozoites that attach to intestinal epithelial cells.
Blood borne protozoa:
• Plasmodium, Trypanosoma, Leishmania
• Are transmitted by insect vectors, in which they replicate before being
passed to new human hosts.
o Toxoplasma gondii -
• Is acquired either through contact with oocyst-shedding cats or by eating
cyst-ridden, undercooked meat.
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 Helminths

• Parasitic worms are highly differentiated multicellular

organisms.
• Their life cycles are complex;
• Most alternate between sexual reproduction in the definitive
host, and
• Asexual multiplication in an intermediate host or vector.

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• Helminths comprise three groups:
1. Round worms (Nematodes)
• Are circular in cross-section and non-segmented.
• Are grouped in to two:
A. Intestinal nematodes include -
A. lumbricoides, Strongyloides stercoralis, and hookworms.
B. Nematodes that invade tissues include -
The filariae, such as Wuchereria bancrofti and Trichinella spiralis

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2. Tapeworms (cestodes)
• Have a head (scolex) and a ribbon of multiple flat segments
(proglottids).
• They adsorb nutrition through their tegument and do not have a
digestive tract.
• They include the fish, beef, and pork tapeworms that make their home
in the human intestine.
• The larvae that develop after ingestion of eggs of certain tapeworms
can cause cystic disease within tissues such as:
Echinoccus granulosus larvae cause hydatid cysts.
Pork tapeworm larvae produce cysts called cysticerci.

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3. Flukes (trematodes)
• Are leaf-shaped flatworms with prominent suckers that are
used to attach to the host.
• They include liver and lung flukes and schistosomes.

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 Ectoparasites

• Includes - Lice, bedbugs, fleas, mites, ticks, spiders.

• That cause disease by biting or by attaching to and living on or in the
skin.
• Infestation of the skin by arthropods is characterized by itching and
excoriations, such as:
 Pediculosis caused by lice attached to hairs, or Scabies caused by
mites burrowing into the stratum corneum.

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TECHNIQUES FOR IDENTIFYING INFECTIOUS
AGENTS
• There are several methods for identifying microorganisms in tissue
and body fluids:
Culture – For Bacterial and fungal infections.
 Histology – by using hematoxylin and eosin (H&E) stained sections.
Serology - by detecting pathogen-specific antibodies in the serum.
Molecular diagnostics - Polymerase chain reaction (PCR) and
transcription-mediated amplification.
Proteomics - Mass spectrometry can be used to identify
microorganisms based on protein content.

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 Techniques for Identifying Infectious Agents

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Routes of Entry of Microbes

• Microbes can enter the host through breaches in the skin, by

inhalation or ingestion, or by sexual transmission.
Skin
 Gastrointestinal Tract
 Respiratory Tract
 Urogenital Tract

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Spread and Dissemination of Microbes Within the
Body
• Some microorganisms proliferate locally, at the site of initial infection,
• Whereas others penetrate the epithelial barrier and spread to distant
sites by way of the lymphatics, the blood, or nerves.
• Microbes can spread within the body in several ways:
Lysis and invasion.
Through blood and lymph.
Cell-to-cell transmission.
• The consequences of blood borne spread of pathogens vary widely
depending on:
The virulence of the organism, the magnitude of the infection, the
pattern of seeding, and host factors such as immune status.
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 Transmission of Microbes
• Every fluid or tissue that is normally secreted, excreted, or shed is used
by microorganisms to leave the host for transmission to new victims.
• These includes:-
Skin.
Oral secretions.
Respiratory secretions.
Stool.
Urine.
Genital tract.
Vertical transmission.
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Classification of Important Sexually Transmitted Diseases

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 SPECTRUM OF INFLAMMATORY RESPONSES
TO INFECTION

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• There are five major histologic patterns of tissue reaction
in infections:

I. Suppurative (Purulent) Inflammation

II. Mononuclear and Granulomatous Inflammation
III. Cytopathic - Cytoproliferative Reaction
IV. Tissue Necrosis
V. Chronic Inflammation and Scarring

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 Mononuclear and
Granulomatous Inflammation
• Diffuse, predominantly mononuclear, interstitial infiltrates are a
common feature of all chronic inflammatory processes,
• But sometimes they appear acutely in response to viruses,
intracellular bacteria, or intracellular parasites.
• In addition, spirochetes and some helminths also provoke chronic
inflammation.
• Eosinophilia can be prominent with some helminthic infections
• Plasma cells are common in the primary and secondary lesions of
syphilis.

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• Granulomatous inflammation is a distinctive form of mononuclear
inflammation usually evoked by:
• Infectious agents that resist eradication, but
• Nevertheless are capable of stimulating strong T-cell–mediated
immunity.
• M. tuberculosis, Histoplasma capsulatum, schistosome eggs.
• Granulomatous inflammation is characterized by accumulation of
activated macrophages called epithelioid cells,
• Which may fuse to form giant cells.
• In some cases, there is a central area of caseous necrosis.
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 Cytopathic - Cytoproliferative
Reaction
• Cytopathic-cytoproliferative reactions usually are produced by viruses.
• The lesions are characterized by cell necrosis or cellular proliferation,
usually with sparse inflammatory cells.
• Some viruses replicate within cells and make viral aggregates that are
visible as inclusion bodies (herpes viruses or adenovirus), or
• Induce cells to fuse and form multinucleated cells called polykaryons
(measles virus or herpes viruses).
• Focal cell damage in the skin may cause epithelial cells to become
detached, forming blisters.

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• Some viruses can cause epithelial cells to proliferate.
• Venereal warts caused by HPV
• Umbilicated papules of molluscum contagiosum caused by
poxviruses.
• Viruses can contribute to the development of malignant neoplasms

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 Tissue Necrosis
• Clostridium perfringens and other organisms that secrete powerful
toxins.
• These toxins can cause rapid and severe necrosis that tissue damage
is the dominant feature.

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 Chronic Inflammation and Scarring

• Many infections elicit chronic inflammation,

• Which can either resolve with complete healing or lead to extensive
scarring.
• For example, schistosome eggs cause “pipestem” fibrosis of the liver
or fibrosis of the bladder wall.
• Tuberculosis causes constrictive fibrous pericarditis.
• Chronic HBV infection may cause cirrhosis of the liver, in which dense
fibrous septa surround nodules of regenerating hepatocytes.

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 Mycobacterium tuberculosis

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 Introduction
• Mycobacterium tuberculosis is responsible for most cases of
tuberculosis;
• The reservoir of infection is humans with active tuberculosis.
• Oropharyngeal and intestinal tuberculosis contracted by drinking milk
contaminated with M. bovis (unpasteurized milk).

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• Bacteria in the genus Mycobacterium are slender, aerobic rods that
grow in straight or branching chains.
• Mycobacteria have a unique waxy cell wall composed of
mycolic acid,
• Which makes them acid fast, meaning they will retain stains even on
treatment with a mixture of acid and alcohol.
• Mycobacteria are weakly Gram positive.

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 Epidemiology

• Tuberculosis is estimated to affect 1.7 billion individuals worldwide,

• With 8 to 10 million new cases and 1.6 million deaths each year.
• Infection with HIV makes people susceptible to rapidly
progressive tuberculosis.
• Over 10 million people are infected with both HIV and M.
tuberculosis.

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• It is important that infection with M. tuberculosis be differentiated
from disease.
• Infection is the presence of organisms, which may or may not cause
clinically significant disease.
• 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.

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 Pathogenesis
• The pathogenesis of tuberculosis in a previously unexposed
immunocompetent person depends on:
• The development of anti-mycobacterial cell-mediated immunity.
• This confers resistance to the bacteria and also results in
development of hypersensitivity to mycobacterial antigens.
• The pathologic manifestations of tuberculosis, such as caseating
granulomas and cavitation,
• Are the result of the hypersensitivity that develops in concert with
the protective host immune response.

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• Immunity to M. tuberculosis is primarily mediated by TH1 cells, which
stimulate macrophages to kill the bacteria.
• This immune response, while largely effective, comes at the cost of
hypersensitivity and accompanying tissue destruction.
• Reactivation of the infection or re-exposure to the bacilli in a
previously sensitized host results in:-
• Rapid mobilization of a defensive reaction but also
increased tissue necrosis.

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 Clinical Features of
Tuberculosis.
• Primary tuberculosis is the form of disease that develops in a previously
unexposed, and therefore unsensitized, person.
• About 5% of newly infected people develop clinically significant
disease.
• The elderly and profoundly immunosuppressed persons may lose
their immunity to M. tuberculosis, and
• May develop primary tuberculosis.
• With primary tuberculosis the source of the organism is
exogenous.

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• In most people, the primary infection is contained, but in others,
primary tuberculosis is progressive.
• Progressive primary tuberculosis more often resembles an acute
bacterial pneumonia,
• With lower and middle lobe consolidation, hilar
adenopathy, and pleural effusion.
• Cavitation is rare, especially in people with severe
immunosuppression.
• Lymphohematogenous dissemination may result in the
development of tuberculous meningitis and miliary tuberculosis.

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• Secondary tuberculosis is the pattern of disease that arises in a
previously sensitized host.
• It may follow shortly after primary tuberculosis, but
• More commonly it appears many years after the initial infection,
usually when host resistance is weakened.
• It most commonly stems from reactivation of a latent infection, but
exogenous reinfection can occur.
• Reactivation is more common in low-prevalence areas, while
reinfection plays an important role in regions of high contagion.

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• Secondary pulmonary tuberculosis classically involves the apex of
the upper lobes of one or both lungs.
• Marked tissue response that tends to wall off the focus of infection.
• The regional lymph nodes are less prominently involved early in
secondary disease than primary tuberculosis.
• Cavitation occurs readily in the secondary form.
• Erosion of the cavities into an airway is an important source of
infection,
• Because the person now coughs sputum that contains bacteria.

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• Low grade and intermittent Fever
• Night sweats occur.
• Increasing amounts of sputum, at first mucoid and
later purulent
• Some degree of hemoptysis
• Pleuritic pain
• Extrapulmonary manifestations

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 Diagnosis

• History of symptom complex

• Physical examinations and radiographic findings of consolidation or
cavitation in the apices of the lungs.
• Acid-fast smears and cultures of the sputum
• Culture remains the gold standard because it also
allows testing of drug susceptibility.
• PCR amplification of M. tuberculosis DNA.

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Morphology.

Primary Tuberculosis.
• Involves lower part of the upper lobe or the upper part of the lower
lobe, usually close to the pleura.
• Ghon focus - a 1- to 1.5-cm area of gray-white inflammation with
consolidation with caseous necrosis at the center.
• Combination of parenchymal lung lesion and nodal involvement is
referred to as the Ghon complex.
• During the first few weeks there is also lymphatic and hematogenous
dissemination to other parts of the body.
• Characteristic granulomatous inflammatory reaction that forms both
caseating and non-caseating
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Secondary Tuberculosis.
• Involves the apical pleura.
• Foci are sharply circumscribed, firm, gray-white to yellow areas that
have a variable amount of central caseation and peripheral fibrosis .
• In immunocomptetent individuals,
• The initial parenchymal focus undergoes progressive fibrous
encapsulation, leaving only fibrocalcific scars.
• Histologically, the active lesions show characteristic coalescent
tubercles with central caseation.
• Immunocompromised people do not form the characteristic
granulomas.
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Progressive pulmonary tuberculosis
• In the elderly and immunosuppressed.
• The apical lesion expands into adjacent lung and eventually erodes
into bronchi and vessels.
• This evacuates the caseous center, creating a ragged, irregular cavity
that is poorly walled off by fibrous tissue.
• Erosion of blood vessels results in hemoptysis.

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Miliary pulmonary disease
• Occurs when organisms draining through lymphatics enter the venous blood
and circulate back to the lung.
• Individual lesions are either microscopic or small, visible (2-mm) foci of
yellow-white consolidation scattered through the lung parenchyma.
• Miliary lesions may expand and coalesce, resulting in consolidation of large
regions or even whole lobes of the lung.
• With progressive pulmonary tuberculosis, the pleural cavity is
invariably involved, and
• Serous pleural effusions, tuberculous empyema, or obliterative
fibrous pleuritis may develop.
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Endobronchial, endotracheal, and laryngeal tuberculosis
• May develop by spread through lymphatic channels or from
expectorated infectious material.
• The mucosal lining may be studded with minute granulomatous
lesions that may only be apparent microscopically.
Systemic miliary tuberculosis
• Occurs when bacteria disseminate through the systemic arterial
system.
• Miliary tuberculosis is most prominent in the liver, bone marrow,
spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis

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Isolated tuberculosis
• Appear in any of the organs or tissues seeded hematogenously and
may be the presenting manifestation.
• Organs that are commonly involved include:
Meninges (tuberculous meningitis),
Kidneys (renal tuberculosis),
Adrenals (formerly an important cause of Addison disease),
Bones (osteomyelitis), and
Fallopian tubes (salpingitis).
Vertebrae/spine - Pott disease
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TB Lymphadenitis
• Is the most frequent presentation of extrapulmonary tuberculosis.
• Usually occurring in the cervical region (“scrofula”).
• In HIV-negative individuals, lymphadenitis tends to be unifocal
and localized.
• HIV-positive people there is multifocal disease, systemic
symptoms, and
• Either pulmonary or other organ involvement by active
tuberculosis.

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Intestinal tuberculosis
• Contracted by the drinking of contaminated milk
• Swallowing of coughed-up infective material in patients with
advanced pulmonary disease.
• Typically the organisms are seed to mucosal lymphoid aggregates of
the small and large bowel.
• Then undergo granulomatous inflammation that can lead to
ulceration of the overlying mucosa, particularly in the ileum.

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 Syphilis

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• Syphilis is a chronic venereal disease with multiple presentations.
• The causative spirochete, T. pallidum
• T. pallidum, is too slender to be seen in Gram stain, but
• It can be visualized by silver stains, dark-field examination, and
immunofluorescence techniques.
• Sexual contact is the usual mode of spread.
• Transplacental transmission of T. pallidum occurs readily, and active
disease during pregnancy results in congenital syphilis.
• T. pallidum cannot be grown in culture.

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• Syphilis is divided into three stages, with distinct clinical and
pathologic manifestations.

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1. Primary Syphilis
• Occurs approximately 3 weeks after contact with an infected individual
• Characterized with a single firm, nontender, raised, red lesion (chancre);
• Located at the site of treponemal invasion on the penis, cervix, vaginal wall,
or anus.
• The chancre heals in 3 to 6 weeks with or without therapy.
• Spirochetes are plentiful within the chancre and can be seen by
immunofluorescent stains of serous exudate.
• Treponemes spread throughout the body by hematologic and lymphatic
dissemination even before the appearance of the chancre.

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2. Secondary Syphilis
• Occurs 2 to 10 weeks after the primary chancre.
• Is due to spread and proliferation of the spirochetes within the skin
and mucocutaneous tissues.
• Secondary syphilis occurs in approximately 75% of untreated
people.
• The skin lesions, which frequently occur on the palms or soles of the
feet, may be maculopapular, scaly, or pustular.
• Condylomata lata
• Silvery-gray superficial erosions may form on any of the mucous
membranes but are particularly common in the mouth, pharynx,
and external genitalia.
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• All these painless superficial lesions contain spirochetes and so are
infectious.
• Lymphadenopathy, mild fever, malaise, and weight loss are also
common in secondary syphilis.
• The symptoms of secondary syphilis last several weeks, after which
the person enters the latent phase of the disease.
• Superficial lesions may recur during the early latent phase, although
they are milder.

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 3. Tertiary Syphilis.

• Occurs in approximately one third of untreated patients, usually after

a latent period of 5 years or more.
• Tertiary syphilis has three main manifestations:
 Cardiovascular syphilis, neurosyphilis, and so-called benign tertiary
syphilis (Gummas).
• These may occur alone or in combination.

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 Cardiovascular syphilis
 In the form of syphilitic aortitis, accounts for more than 80% of cases of
tertiary disease.
 The aortitis leads to slowly progressive dilation of the aortic root and
arch,
 Which causes aortic valve insufficiency and aneurysms of the proximal
aorta.

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.Neurosyphilis
 May be symptomatic or asymptomatic.
 Symptomatic disease manifests in several ways:
 Chronic meningovascular disease.
 Tabes dorsalis.
 Generalized brain parenchymal disease called general paresis.

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 Asymptomatic neurosyphilis
Accounts for about one third of neurosyphilis cases
Detected when a patient's CSF exhibits abnormalities,
Such as pleocytosis (increased numbers of inflammatory
cells), elevated protein levels, or decreased glucose.

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 Benign tertiary syphilis
• Characterized by the formation of gummas in various sites.
• Gummas are nodular lesions probably related to the
development of delayed hypersensitivity to the bacteria.
• They occur most commonly in bone, skin, and the mucous
membranes of the upper airway and mouth.

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 Congenital Syphilis

• Congenital syphilis occurs when T. pallidum crosses the placenta from

an infected mother to the fetus.
• Maternal transmission happens most frequently during
primary or secondary syphilis, when the spirochetes are
most numerous.
• Intrauterine death and perinatal death each occurs in approximately
25% of cases of untreated congenital syphilis.

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• Manifestations of congenital disease are divided into:
 Early (infantile) and late (tardive) syphilis, depending on whether
they occur in the first 2 years of life or later.
• Early congenital syphilis is often manifested by nasal discharge
and congestion (snuffles) in the first few months of life.
• A desquamating or bullous rash can lead to sloughing of the
skin, particularly of the hands and feet and around the
mouth and anus.
• Hepatomegaly and skeletal abnormalities are also common.
• Nearly half of untreated children with neonatal syphilis will develop
late manifestations.
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 Serologic Tests for Syphilis
• Serology remains the mainstay of diagnosis, although microscopy
and PCR are also useful.
• Serologic tests include:
• Non-treponemal antibody tests and treponemal antibody tests.
.

• Serologic response may be delayed, absent, or exaggerated (false-positive results) in people co-infected with
syphilis and HIV. However, in most cases, these tests remain useful in the diagnosis and management of syphilis
even in people infected with HIV

 False-positive VDRL test results are common and are associated with certain acute
infections, collagen vascular diseases (e.g., systemic lupus
erythematosus), drug addiction, pregnancy, hypergammaglobulinemia
of any cause, and lepromatous leprosy.

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1. Non-treponemal tests
• Measure antibody to cardiolipin
• Cardiolipin is a phospholipid present in both host tissues and T.
pallidum.
• Rapid plasma reagin tests
• Venereal Disease Research Laboratory (VDRL) tests.
• Typically become positive 4 to 6 weeks after infection .
• Nearly always positive in secondary syphilis,
• They usually become negative in tertiary syphili s.
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2.Treponemal antibody tests
• Measure antibodies that specifically react with T. pallidum.
• Fluorescent treponemal antibody absorption test
• Microhemagglutination assay for T. pallidum antibodies.
• These tests also become positive 4 to 6 weeks after infection
• Remain positive indefinitely, even after successful
treatment.
• More expensive than non-treponemal tests.
• More specific than the non-treponemal tests.
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Morphology
o In primary syphilis:
• Chancre - Slightly elevated, firm, reddened papule, that erodes to create a
clean-based shallow ulcer.
• Treponemes are visible at the surface of the ulcer with
silver stains (e.g., Warthin-Starry stain) or
immunofluorescence techniques.
• Intense infiltrate of plasma cells, with scattered macrophages and
lymphocytes and a proliferative endarteritis.

The regional nodes are usually enlarged due to nonspecific acute or

chronic lymphadenitis, plasma cell–rich infiltrates, or granulomas.
The endarteritis,
15/11/13 which is seen in pathology
all stages of
of infectious syphilis, starts with endothelial cell
disease 85
o In secondary syphilis:
• Widespread mucocutaneous lesions involve the oral cavity,
palms of the hands, and soles of the feet.
• Red lesions in the mouth or vagina contain the most
organisms and are the most infectious.
• Plasma cell infiltrate and obliterative endarteritis as the
primary chancre.
• Inflammation is often less intense.
• The rash frequently consists of discrete red-brown macules less
than 5 mm in diameter, but it may be follicular, pustular, annular, or
scaling.
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o Tertiary syphilis
• Most frequently involves the aorta,CNS, liver, bones, and testes.
• The aortitis is caused by endarteritis of the vasa vasorum of the
proximal aorta.
• Occlusion of the vasa vasorum results in scarring of the media of the
proximal aortic wall, causing a loss of elasticity.
• Neurosyphilis takes one of several forms, designated
meningovascular syphilis, tabes dorsalis, and general paresis.

15/11/13 pathology of infectious disease 87

• Syphilitic gummas:
• White-gray and rubbery, occur singly or multiply, and vary in size from
microscopic lesions to large tumor-like masses.
• Occur in skin, subcutaneous tissue, liver, bone, and joints.
• Histologically gummas consists:
• Centeral coagulative necrosis
• Marginal palisading macrophages and fibroblasts surrounded by large
numbers of mononuclear leukocytes, chiefly plasma cells.
• Treponemes are scant in gummas
• In the liver, scarring as a result of gummas may cause a
distinctive hepatic lesion known as hepar lobatum.
15/11/13 pathology of infectious disease 88
o Congenital syphilis
• More severe rash than that of adult secondary syphilis.
• It is a bullous eruption of the palms and soles of the feet associated with
epidermal sloughing.
• Syphilitic osteochondritis and periostitis affect all bones, but lesions of
the nose and lower legs are most distinctive.
• Destruction of the vomer causes collapse of the bridge of the nose and, later
on, the characteristic saddle nose deformity.
• Periostitis of the tibia leads to excessive new bone growth on the anterior
surfaces and anterior bowing, or saber shin.
• Widespread disturbance in endochondral bone formation.
• The epiphyses become widened as the cartilage overgrows, and cartilage is
found in displaced islands within the metaphysis.
15/11/13 pathology of infectious disease 89
• The late manifestations of congenital syphilis include:
 A distinctive triad of interstitial keratitis, Hutchinson
teeth, and eighth-nerve deafness.
• Other ocular changes include choroiditis and abnormal retinal
pigmentation.
• Hutchinson teeth are small incisors shaped like a screw driver or a
peg, often with notches in the enamel.
• Eighth-nerve deafness and optic nerve atrophy develop secondary
to meningovascular syphilis.

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15/11/13 pathology of infectious disease 91