Syphilis

SYPHILIS

Morphology of Treponema pallidum subsp. pallidum

 Causative agent of SYPHILIS  Fine spiral organism with 3 periplasmic    

flagella 10-13 coils Appears white against a dark background Microaerophilic; survives longer in the presence of 3-5% oxygen Composed of phospholoipids bilayer and protein antigens – outer membrane

Scanning Electron Micrograph of T. pallidum

Mode of Transmission  Organism is very fragile, destroyed

rapidly by heat, cold and drying; susceptible to disinfectants  Sexual transmission most common, occurs when abraded skin or mucous membranes come in contact with open lesion.  Can be transmitted to fetus.  Rare transmission from needle stick and blood transfusion.

 Has a remarkable tropism to arterioles

(endarteritis)  2 types of antibodies produced: treponemal and nontreponemal (reagin) 1. Non Treponemal Abs REAGIN – an anti-cardiolipin Ab, reacts with lipid Ags 2. Treponemal Abs – directed against pathogenic T. Pallidum and closely related strains a. Group antibodies – directed against group antigens b. Specific Treponemal Antibodies – specific for each treponemal antigen

 Antigen

1.Wassermann Antigen  Cardiolipin - a normal constituents of host tissue - is a hapten and is bound to the microbial cell in order to be antigenic -a phospholipid  Pathogenic treponemes growing in vivo INCORPORATES this plentiful supply of phospholipid  Microbial cell/ treponemes- is the foreign carrier  Bound phospholipid(cardiolipin)- is the antigenic determinant

2.TREPONEMAL ANTIGEN Reiter CHON (group antigens) - a protein found in most treponemes (both in saprophytic and pathogenic treponemes) Specific Treponemal Antigens - specific for each treponeme species

Clinical Infection

 Syphilis

- French disease/Italian disease/ The Great Pox - also known as the “great imitator” - a disease of blood vessels and of the perivascular areas; can cross the placenta - it is characterized by chancre, fever, sore throat, headache and rash[palms and soles], gummas in skin, neurosyphilis -if untreated, T. Pallidum can

Stages of Disease  Primary  Secondary  Latent  Tertiary  Congenital Syphilis

Primary Syphilis  Organism enters directly through skin

or through mucosal tissue.  Carried by blood throughout the body.  Organisms remaining at the site begin to multiply.

Primary Syphilis Chancre

 Variable incubation period of 10 days to

several months, a primary lesion, chancre, forms at the entrance site.  Chancre begins as a small, usually singular nodule; as it enlarges, the overlying epithelial tissues begins to necrose, resulting in a relatively painless ulcer.  Unlike other bacterial infections, there is no formation of pus unless a secondary bacterial infection sets in.

Primary - Chancre

 Chancre is most frequently seen on the

external genitalia

 In women the lesions may form in the vagina

or on the cervix.  In men it may be inside the urethra, resulting in a serous discharge.

 The lesion heals spontaneously after 1-5

weeks.  Swab of chancre smeared on slide, examined under dark-field microscope, spirochetes will be present.  Thirty percent become serologically positive one week after appearance of chancre, 90% positive after three weeks.

Penis: The most common sites of infection in men are on the penis. Within 90 days of infection (three week average), a painless sore or ulcer called a chancre appears.  This chancre contains a clear fluid that is full of syphiliscausing bacteria making you highly contagious. The chancre will heal even without treatment within a few weeks.

Primary Syphilis - Chancre

Primary Syphilis - Chancre

Fluid From Chancre

Spirochetes in Blood

Secondary Syphilis  Occurs 6-8 weeks after initial chancre,

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becomes systemic, patient highly infectious. Characterized by localized or diffuse mucocutaneous lesions, often with generalized lymphadenopathy. Primary chancre may still be present. Secondary lesions subside in about 2-6 weeks. Serology tests nearly 100% positive.

Secondary Syphilis  A widespread eruption resembling

psoriasis or pityriasis rosea which prominently involves the hands should always include the differential diagnosis of secondary syphilis.

Secondary Syphilis  Secondary syphilis lesions on back

Around the Mouth: Secondary symptoms can include multiple sores on the penis, anus or around the mouth.  They can also be found in the throat, which cannot be readily seen.

Wart Like Growths: hair loss, white patches on your tongue or multiple wartlike growths called condylomata lata.ike Growths: hair loss, white patches on your tongue or multiple wart-like growths called condylomata lata

Latent Syphilis  Stage of infection in which organisms

persist in the body of the infected person without causing symptoms or signs (asymptomatic).  This stage may last for years.  One-third of untreated latent stage individuals develop signs of tertiary syphilis.  After four years it is rarely communicable sexually but can be passed from mother to fetus.

Tertiary Syphilis  Divided into three manifestations:  Gummatous syphilis  Cardiovascular syphilis  Neurosyphilis

Tertiary Syphilis Gummatous

 Gummas are localized areas of

granulomatous inflammation found on bones, skin and subcutaneous tissue.  Cutaneous gummas may be single or multiple, generally asymmetric and grouped together.  Visceral lesions often cause local destruction of the affected organ.  Contain lymphocytes, plasma cells and perivascular inflammation.

Tertiary Syphilis Buboe of Neck

Tertiary Syphilis

Tertiary Syphilis Gumma

Tertiary Cardiovascular

 This condition appears 20 or more years

post-infection.  Usually involves the aorta.  Invading treponemes cause scarring of the tunica media.  Over many years, the inflammatory scarring weakens the aortic wall, leading to aneurysm formation, which causes incompetence of the aortic valve and narrowing of the coronary ostia.

Tertiary Cardiovascular

 Antibiotic treatment cures the

syphilis infection and stops the progress of cardiovascular syphilis.  The damage that has already occurred may not be reversed.

Neurosyphilis  Caused by invasion of organisms into

the CNS.  Manifests as an insidious but progressive loss of mental and physical functions and is accompanied by mood alterations.  General paresis of the insane:  forgetful,  personality change,  psychiatric symptoms.

 Onset usually 10-20 years after primary

infection.  Treatment may not improve symptoms.

Neurosyphilis  Neurological complications at this stage

include generalized paresis of the insane which results in personality changes, changes in emotional affect, hyperactive reflexes.  Tabes dorsalis, degeneration of lower spinal cord, general paresis and chronic progressive dementia often results in a characteristic shuffling gait.  Can only be diagnosed serologically by VDRL.

Neurosyphilis  Cerebral atrophy, most prominent in

frontal lobes seen in general paresis.

Congenital Syphilis  Transmitted from mother to fetus.  Fetus affected during second or third

trimester.  Forty percent result in syphilitic stillbirth-fetal death that occurs after a 20 week gestation and the mother had untreated or inadequately treated syphilis at delivery.

Congenital Syphilis  According to the CDC, 40% of births

to syphilitic mothers are stillborn.  40-70% of the survivors will be infected, and 12% of these will subsequently die prematurely  Death from congenital syphilis is usually through pulmonary hemorrhage.

Congenital Syphilis  Bone deformities  Blindness  Deafness  Deformed faces  Dental deformities  Skin rashes  Neonatal death

Congenital Syphilis  Live-born infants show no signs

during first few weeks.  Sixty to 90 % develop clear or

hemorrhagic rhinitis.  skin eruptions (rash) especially around mouth, palms of hands and soles of feet.

 Other signs: general

lymphadenopathy, hepatosplenomegaly, jaundice, anemia, painful limbs, and bone abnormalities.

Congenital Syphilis  Early onset syphilis manifests at birth or

months after, exhibiting a diffuse infiltration, scabs and fissuring along the periphery of the mouth, which leave sulci in a radiated pattern or rhagades

Congenital Syphilis  clear or hemorrhagic rhinitis

Congenital Syphilis  Skin eruptions (rash) especially around

mouth, palms of hands and soles of feet

Congenital Syphilis  Hutchinson’s incisors.

SEROLOGIC TESTS FOR SYPHILIS

1.NonTreponemal methods/ Reagin Tests for Syphilis A. VDRL (Venereal Disease Research

Laboratory Test) -uses heated serum (@56ºC for 30min.) as specimen and result is read microscopically PRINCIPLE: FLOCCULATION (agglutination of colloidal particles) Colloidal suspensions of lipoids + REAGIN (+) flocculation

- Rgt Ag: colorless alcoholic solution

containing cardiolipin, lecithin, cholesterol - Rotator: 180rpm for 4 minutes - False (+) VDRL result: SLE, rheumatic fever, IM, malaria, pregnancy Results: no clumping (or slight roughness): nonreactive small clumps: weakly reactive medium or large clumps: reactive

Rapid plasma reagin  -uses unheated serum as specimen 

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and the result is read microscopically - uses the incorporation cholinechloride to modify the basic VDRL antigen and allows testing of plasma without preliminary heating -Principle: FLOCCULATION -Rgt Ag: colorless alcoholic sol’n containing cardiolifin lecithin cholesterol with charcoal -Rotator: 100 rpm for 8 mins

2. Treponemal Mtds/Specific Mtds

 TPI (T. Pallidum Immobilization Test)

-test of choice for CSF specimen when regain give NR results -Principle: The antibody produced against T. Pallidum plus complement can immobilize the live treponemes. -Rgt ag: live actively motileT.pallidum organisms (extracted from lessions of infected rabbits) -Ab:Patient syphilitic serum -Complement: guinea pig complement -(+) result: immobilization of treponemes (>50% immobile)

(Fluorescent Treponemal Antibody Absorpion Test)  Principle: Indirect Fluorescent    

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immunoassay Rgt ag: Dead T.pallidum (Nichols strain) dried and fixed on slide Ab: patient syphilitic serum Absorbent: Reiter treponemes *patient serum is prediluted in a heated culture filtrate of Reiter Treponemes so that grouped antibodies are blocked and the specific antibody will be then free to bind with the Treponemal antigen. Conjugate: Fluorescent-labeled AHG

FTA-ABS Step 1  Teponema pallidum, the known

antigen, is fixed to a microscope slide.

FTA-ABS – Step 2  If there are antibodies against Treponema

pallidum in the patient's serum, they will bind to the spirochete.  All other antibodies are washed from the slide.

FTA-ABS- Step 3

 Fluorescent anti-human gamma globulin (anti-

HGG) is added to the well.  The anti-HGG will bind with human IgG antibodies bound to the Treponema pallidum on the slide.  All unbound anti-HGG is washed from the slide.  Viewed with a fluorescent microscope, the spirochetes will fluoresce

Positive FTA Test for Syphilis Viewed with a Flourescent Microscope

T.Pallidum Hemeagglutination Test

 Principle: Hemeagglutination  Uses RBC coated with treponemal

antigen to detect patients treponemal antibodies  Rgt ag: glutaraldehyde stabilized turkey RBC coated with treponemal antigen  Antibody: patients syphilitic serum  (+) result: hemeagglutination

MHA-TP (Microhemeaggutination T. Pallidum Test)  PRINCIPLE: HEMEAGGLUTINATION  Uses RBC coated wih Treponemal

antigen to detects patients treponemal antibodies  Rgt Ag: tanned formalin sheep RBC coated with treponemal antigen  Ab: Patient’s syphilic serum  Positive result : hemagglutination