4. MORPHOLOGY
• Gram negative bacilli, cockscrew-shaped
• Slender spirals: length 5-15um * 0.2um
• regular tight coils at l um intervals 8-
14/cell
• Active motility around flagellum by
attaching to tissue by tapering end, secrete
hyaluronidase
• Sluggish, drifting; active motility
5. structure
• Outer sheath or glycosaminoglycan coat
• Outer membrane…PPG/structural integrity
• Periplasmic space inside for endoflagella
• Endoflagella start at ends, overlap in mid
Wind around axil
• Inner membrane; osmotic stability
• Protoplasmic cylinder
6. GROWTH
• T pallidum: In Vitro not grown:
non pathogenic Rieters strain can be grown
• Can Maintain at 25 C , 4-7 days
anaerobic,albumin,NaHCO3,pyruvate,serum
• Rabbit epitheleal cells:
multiply several generations 10-100
• Division:
transverse fission : doubling time 30hours
• Microaerophilic 1-4% O2
• Blood:Transfusiontransmissionstore2-6Cfor3-5days/low risk,screeneddonors.survive 24hrs 4c
7. HISTORICAL NAMES
Great pox" in the 16th
century
• Scotland, Grandgore
• French army outbreak morbus gallicus French dis
. OR the la maladie anglaise (the English Dis
• Italians called it "Spanish disease", & “Italian
disease" or “Neapolitan disease”,
• Russians called it : “Polish disease",
• Arabs called it the "Disease of the Christians”.
terms "lues" and "Cupid's Disease" were used.
8. HISTORY
• ORIGIN
• Europe 15 century Mediterranian-epidemic
• New World Columbus crew got it West Indies, so
reached Spain
• Africa endemic for centuries-Europe by armies &
civil populations
• 18 Century d/d gonorrhea
• 1905,Schaudinn and Hoffman etiologic agent
• 1906 Wassermann serological tests introduced
9. TRANSMISSION
1.Intimate Contact with infected person,
• From spirochete containing lesion of
skin/mm (genitalia, mouth, rectum) to
skin/mm
• Sexual/accidental; physician, pathologist
2. Pregnanat woman to fetus
3. Blood transfusion
• Site of Inoculation: Genetalia/genital tract
• Survival outside host: limited
10. PATHOGENESIS
• No enzymes & toxins produced
• Infects endothelium of small BV called “
Endarteritis
affects BV of brain & CVS seen in tertiary syphilus
Perivascular areas affected.
After invasion organisms multiply and disseminate
rapidly and widely via the above routes
11. PRIMARY SYPHILUS
• CHANCRE or ULCER: painless
• In 3 weeks at inoculation site ;
• shallow, well defined, indurated edges, red
surface, exude serum
• profuse shedding of T.pallidum.
• accumulation of mononuclear WBC, lymph,
plasma cells; capillary endothelium swells.
• Regional L Nodes enlarge
• Resolution by fibrosis in 3-6 weeks
12. CLINICAL MANIFESTATION
ACQUIRED SYPHILIS
• Human host, sexual contact
• External genitalia: Abraded skin & intact mm
• Other sites: 10-20%
• PRIMARY LESION: 2-10 WEEKS
PAPULE: Local multiplication, breaks to ulcer
HARD CHANCRE: hard base
Inflammatory cells: lymphocytes & plasma cells
20. Latent syphilis
LATENT DISEASE:
Early-latent ----------< 2 yrs of infection;
Late latent----------- > 2 yrs
Pt no symptom but is sero-reactive
not effected by therapy .
Untreated: 40% with symptom; 60% no symptom
• Sequelae of Syphilis 30% cure,
• 30% latent,
• 40% tertiary
21. SEQUAELAE
1 Spontaneous cure; no t/m
• 1/3 primary & secondary cases
2 Latent: 1/3
No lesions appear but serological tests
positive denoting infection.
EARLY LATENT: lasts 1-2 yrs of secondary
stage, symptoms may reappear & pt
infective
22. LATE STAGE OR TERTIARY
SYHPILIS 30% UNTREATED
PTS
• Duration: lasts many years; 3-10 yrs after 2 sta
• Sparse spirochetes
1. GUMMAS;
• benign tertiary syphilis
• bone, skin organs-liver, stomach
• dermal lesions,
• immunologic reaction
25. CONGENITAL SYPHILIS
• : Transplacental infection 10-15 wks
spirochetes enter blood of dev fetus and
disseminate 700 cases; 1988 USA
• Mortality untreated: 25% miscarriage, still
Late stigmata; 40% hepato-splenomegaly,
jaundice, anaemia, pneumonia, snuffles
bone, skin lesions.Hutchison teeth,saber
shin, saddle nose, frontal boss, 8 nerv deaf
26. SEROLOGICAL RESPONSE
Primary syphilis
• AB: 1-4 weeks after chancre. FTA-ABS + first ,
• followed 1 week later by trep.specific tests &
cardiolipin tests.
Secondary syphilis ; all positive
• Latent: Reactivity of cardiolipin decrease
• Late syphilis cardioloipin: reactive/weak/non
reactive; specific trep tests remain +, titre low
27. LABORATORY DIAGNOSIS
SPECIMENS
1 SEROUS FLUID chancre, secondary
skin lesions (moist areas) motile T pallidum
spirochetes seen in primary, secondary, early
congenital, infectious relapsing syphilis.
• Within a few hours of taking AB , treponemes
disappear, so ask pt. of H/O drugs.
2. BLOOD: 3-5ml serum/plasma
(should not hemolysed, lipemic, contaminated).
• CAUTION: GLOVES,SAFE WASTE DISPOSAL
28. • 1 MICROSCOPY
• Dark field direct vision ; viable & actively
motile in primary & active secondary lesion
• Direct Florescent antibody; DFA
exudate taken on slide or capillary
tube
• Special stains
• 2 Animal inoculation 10-100generations in
rabbit
• 3 SEROLOGICAL REACTIONS
35. REAGINIC AB
• REAGIN is a mixture of IgM & IgG AB
• Formed against Cadiolipin-cholestrol-
lecithin.
• Cardiolipin is an important component of
treponemal Ag
• Cardiolipin also extracted from normal
mammalian tissue eg beef heart; so cross
reactions
36. NON SPECIFIC CARDIOLIPIN
REAGIN TESTS
• SCREENING TESTS:
• VDRL:
Heat inactivated serum (to destroy
complement) is reacted with freshly
prepared cardiolipin- cholestrol-lecithin Ag
and resultant flocculation read
microscopically by 10x.
• Quantitation done by double dilution
37. RAPID PLASMA REAGIN
RPR
• Plasma/serum can be used
• CCL Ag has choline chloride added.
No heat-inactivation needed
• Carbon added to Ag which are trapped in
floccules on a card.
• Result read Macroscopically .Can quantify
• Ag stable, ready to use state –6months at 4-
10 C
38. TOULIDINE RED UNHEATED
SERUM TEST(TRUST)
• Red instead of black particles of RPR used to
visualise the reaction.
• Red particles caught in mesh of Ag &AB complex
• Result in few minutes if agitated
• can keep room temperature.
39. FALSE POSITIVE
REACTIONS
• Biological false positive ( BFP )reactions
• Low titres 1/8 or < infections, immune disorders.
• Non-treponemal tests & Reaginic Ab reacts with
200 other Ag
• Transient < 6 months BFP: Malaria, hepatitis
virus pneumonia, viral exanthemas, pregnancy
trypanosomiasis, vaccinations. Titre 1:8
• Long term BFP
SLE, RA, TB, leprosy, cancer, narcotics addict.
40. INCORRECT RESULTS BY
NON SPECIFIC CARDIOLIPIN
TEST• PROZONE:
V. high cardiolipin titres as in secondary
syphilis. Excess AB prevents normal reaction,
False negative or non reactive, rough , grainy
reaction. Perform with undiluted and I:20 diluted
• Incorrect test performance
• HIV: Immunosuppression –non reactive
B cell activation – prozone
No fall in titre after T/M due to
HIV coinfection
41. Benefits of non treponemal tests
• Widely available
• Automation & can be done in large
numbers
• Low cost
• Quantified: diagnostic & therapeutic
evaluation
DRAWBACK
Not sensitive in early syphilis; + in few weeks
42. INTERPRETATION
• Non specific AB to cardiolipin formed in 3-
5 weeks of infection, or 2 weeks after
chancre.
• Secondary syphilis maximum AB,100%
reactivity
• Negative : late, latent syphilis &
with t/m titre falls
after 6 months of primary &
12-18 months of secondary syphilis
43. SPECIFIC TREPONEMAL
TESTS
• Confirm non trep tests & in late syphilis
• NO BFP; IgG persist long i.e years even after
T/M; Rapid, easy to perform & inexpensive
1. TPHA : T.pallidum haemagglutination assay
2. TPPA : T.pallidum particle agglutination assay
3. IC (Immuno-chromatographic): Rapid strip test
4. Latex agglutination: Syphilis fast test
5. FTA-ABS:
(Flourescent treponemal antibod absorption test)
6. EIA (enzyme immunoassays)
44. Treponemal tests
• Done to determine if non-treponemal test
truly or falsely positive
• If both positive, pt has syphilis
• Not useful as screening tests as once +,
life long positive, independent of therapy
• No dilution done; so reactive/non
reactive/inconclusive
• Costly esp when large no donors screened
45. TPHA
• POSITIVE IN PRESENT & PAST INFECTION
• Titres detected in 4th
week or longer
• Primary syphilis: low titres 80-320
• Secondary syphilis high 5120 or >
• Late/latent syphilis drop in tires but still positive
20-30 yrs after T/M
• Microtitration plate coated with sheep or avian
RBC sensitized/coated with T.pallidum Ag
(Nicholes strain)Add serum .Agglutination- matt,
nonagglut-button. (AB to commensal Trep.
Removed by non-pathogenic Reiter’s treponemes)
46. HEMAGGLUTINATION TEST
• Automated, easy , inexpensive, specific,
sensitive
• IgM-FTA-ABS TEST
Congenital syphilis:
• Passive AB maternal
• Fetal active infection IgM
• Not reliable, so abandoned.
47. TPPA & IC
• Gelatin particles used instead of RBC, stability
better
• Positive clumping seen
• Modification: capillary whole blood used instead
of venous
• IC: Rapid 15 minutes, simple, low cost for
specific AB to Trep pallidum (recombinant Ag)
in serum, plasma. 100ul serum in tube , strip
immersed and look for 2 pink bands in +
48. LATEX SYPHILIS FAST TEST
• Latex coated with Trep.pall Ag added to 20
ul serum on a card. Positive test in 8 mins
TREATMENT
• Pencillin 0.03units/ml single I/M injection
• treponemicidal < 1yr duration
• Older/latent disease 3 doses at weekly
interv
• Congenital: i/v
49. OTHER SPECIFIC TESTS
• T.P Immobilization Test(TPI) A suspension of
living & motile treponemes maintained in rabbit
testes are immobilized by reaginic antibody and
complement, seen by dark field microscopy.
Difficult,expensive and false + for non venereal
treponemes.Done in research labs to compare
other tests
• RIETER PROTEIN COMPLEMENT FIXATION
TEST;Ag extract of non virulent strain Reiter
cultured in vitro. Group Ag ;false +/-
50. FLOURESCENT ANTIBODY
TEST in reference lab
• First test to be positive in 3-4 weeks in Primary
sphilis
• Trep.antibody detected by flourescein labeled anti
human antibody
• Used; congenital syphilis, late stage syphilis,
positive reaginic test
• Sensitive, reliable
• FTA;( Florescent Tryp. Antibody test)Nichol’s
strain organisms used as AG ,fixed on slide,test
serum applied,allowed to react. Then layered by
fl.antihuman AB seen by fl.microscope
• Expensive, time consuming
51. CONGENITAL SYPHILIS
• INFANTS: Symptoms suggestive
• Skin lesion/nasal discharge: motile treponemes by
dark field microscopy
• Serology Reactive specific test at 3 months ,
maternal IgG
• Active Infection IgM raised
Higher AB titre than mother and
continues to rise
• MOTHER ; AB tested with infants
52. TREATMENT
• PENCILLIN MIC 0.004U/ml
• Most sensitive organism but R increasing
• Early syphilis 0.03 units/ ml serum 7-10 days
totally arrests disease
• Late 21 days
• Erythromycin, tetracycline, cephaloridin but less
passage to fetus so cong.syph can occur
• Evaluate: 3 months quantitative cardiolipin tests
• Relapse titre increases
53. PREVENTION
• AIDS association so avoid drug abusers,
STD pts, HIV pts
• T/M case contacts, examine them, treat as
primary syphilis as long incubation gives
time for prevention.
