A 29-year-old man presented to an STD clinic complaining of multiple papules on his genitals. Examination revealed indurated papules that were painless. Tests determined it was a case of primary syphilis caused by the bacterium Treponema pallidum.
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1. A 29 year old man came to the
STD clinic complaining of multiple
papules in his gentials. These
papules quickly eroded and
become tough.
He later admitted to
having unprotected
sex with as ex
worker
2. There was regional
lymphadenopathy with
moderately enlarged,
firm, non suppurative,
painless lymph nodes or
satellite buboes.
O/E we noticed papules which
were indurated. It was painless.
3. So from the above case what can we
assume
Its an STD
4. There after various tests
It was found to be a case of Primary Syphilis
Syphilis comes under
8. Ultrastructure
Lipid rich outer membrane- Increased
susceptibility to detergents
Show hardly any antigenic variations
Saprophytic spirochetes are generally coarser.
Endoflagella lie inside outer
membrane and inserted at
tapering portion
11. Cannot be grown in artificial culture media
Cannot determine metabolic, physical and
pathogenic features.
Non pathogenic trep is Reiter strain and Noguchi
strain.
Virulent strains(eg. Nichols strain) has been
maintained by serial passages in rabbit testicles
Recently grown in tissue cultures of rabbit
epithelial cells
12. Epidemiology
Modes of transmission
Sexual contact
Placenta
Kissing
Close contact
Contaminated fresh blood
Fantastic history of syphilis with exact source
not known.
All known contacts post diagnosis needs to be
considered.
13. Blood vessel and lymphatics
Enters blood and
dissipates to various
organs in the body
Pathogenesis
Untreated Syphilis- Progress from
1. Primary
2. Secondary
3. Latent
4. Tertiary stages
14. Clinical features ( contd )
Veneral syphilis
Organism divides 30-33 hours.
Generally incubation period a month.
Early spirochetemia inevitably
develops during this phase
Left untreated at least 2/3
spontaneously clear
1/3 progress
15. Those that progress after 3 weeks
Bacteria multiply at initial entry site and progress to
form a chancre on the genital.
Painless chancre
Usually single except immunocompromised patients
Superficial Ulcer has clean appearance and no exudate.
Painless or slightly tender to touch
16. Primary syphilis
Indurated and superficially ulcerated
Base usually smooth, borders raised and firm and cartilaginous consistency.
Known as Hard chancre
Most common site penis, cervix or labia and anal canal, rectum or
mouth
Regional lymphadenopathy consisting of enlarged, firm, non suppurative,
painless lymph nodes or satellite buboes accompanies primary lesion
Chancre heals within 3-6 weeks and 2-12 weeks later the symptoms of
secondary syphilis develops
17. Secondary syphilis
Clinically most florid stage of infection
Involves skin
Multiplication and wide dissemination of
spirochete and last until sufficient host response
develops to exert some immune control.
Begins 2-8 weeks after appearance of chancre.
18. Secondary syphilis
Nonpruritic macular, maculopapular, papular or
pustular lesions. Begin on the trunk and
proximal extremities. Any surface area becomes
involved.
Macules evolve to papules. Other sites palms,
soles, hair follicles.
19. Secondary syphilis
Warm, moist intertriginous areas ( perianal
area, vulva, scrotum, inner aspects of thigh, skin
under breast) papules enlarge, coalesce and
erode to produce
painless, broad, moist, gray-
white to erythematous highly infectious plaques
termed condylomata lata
21. Secondary syphilis
Constitutional symptoms are seen
CNS involved in 40 % of patients. ( Headache
and meningismus).
Any organ involved, eg with
Renal involements,
syphilitis hepatis
proctitis,
Git
Panuveitis
ostieits, and otosyphilis.
22. Latent syphilis
Period of quiescence.
No clinical manifestation
Serological tests.
Individuals with late latent syphilis are not
considered infectious.
May still transmit infection.
Early latent syphlis is when clinical relapse
occurs.
Diagnosis during this period using serological
tests.
23. Late syphilis
Slowly progressive destructive inflammatory
disease that can affect any organ in body to
produce clinical illness 5-30 or more years after
initial infection.
Neurosyphilis
Cardiovascular syphilis
Gummatous- rare granulomatous lesion of
skeleton, skin and mucocutaneous tissues
24. Congenital syphilis
Women with early syphilis can infect her fetus
much more commonly(75-90%) than with
syphilis over 2yrs duration(35%)
Lesions of congenital- develop 4th month of
gestation when fetal immune competence starts
appearing (suggests pathogenesis requires
immune response from fetus)
Congenital syphilis prevent if given adequate
treatment
Abortions normal.
25. NON-VENEREAL SYPHILIS
Occupationally in doctors or nurses the natural
evolution is as in venereal syphilis, except that
the chancre is extragenital, usually on fingers
In syphilis transmitted by blood transfusion,1
chancre does not occur
Transplacental transmission-any stage of
pregnancy
27. Specimen
Collected with care.
Lesion cleared with a guaze soaked in warm
saline & the margins gently scraped
Gentle pressure applied to the base of lesion &
serum that exudes is collected
Blood also is taken
Serous transudate from moist lesions- Primary
chancre, condyloma latum or mucous patch
28. Direct examination
Primary, secondary and early congenital
syphilis- Immunostaining, PCR, darkfield
examination
Wet film prepared by exudate examined under
dark ground microscope
Needs to be differentiated from saprophytes
Not specific and requires 104 per ml of
spirochetes.
29. In case lesions is cleaned with antiseptic-Direct
immunofluorescent antibody staining and
immunohistochemical staining better.
Best observed from chancre, condyloma and
mucous patches.
3 negatives before final.
30. Biopsy specimen
Warthin starry stain.
Levaditi and Fontaina method are silver staining
methods.
Preferred methods of staining is
immunohistochemical staining.
31. MAJOR SEROLOGICAL TESTS FOR SYPHILIS
A.Non-specific(Reagin Ab) tests using cardiolipin Ag (STANDARD
TESTS FOR SYPHILIS)
oWasserman complement fixation reaction
oKahn flocculation test
oVDRL test
oRapid plasma reagin(RPR)
oAutomated RPR
oVDRL-ELISA test
B. Group specific test using cultivable treponemal(Reiter strain) Ag
oReiter protein complement fixation(RPCF) test
33. VDRL TEST FOR SYPHILIS
Type of slide flocculation test
In this inactivated serum(heated at 56c for 30
mins) is mixed with cardiolipin Ag on a special
slide & rotated for 4 mins
Cardiolipin forms visible clumps on combining
with reagin Ab
Reaction read under low power microscope as
reactive, weak or non.
Monitor patients response to therapy
34. RPR
Common test in labs now.
Employs carbon particles and read
macroscopically.
Black carbon particles are bound to caridolipin,
when mixed with positive serum on disposable
card.
Agglutination is easily observed.
Prozone phenomenon in upto 2% of cases
especially in secondary and pregnancy
36. RPR
Advantages
Enables the result to be read by eye
Useful in field studies
RPR done with unheated serum or plasma
Fingerprick sample is sufficient
Dis advantages
Cant test CSF
37. Trust-Toloudine red unheated serum test.
Instead of carbon particle we use toloudine red
Automated reagin antibody test-
38. 4 fold change in titre important.
Highest prevalence during secondary syphilis.
Quantitative test should become non reactive 1
year after treatment in primary and 5 years in
secondary.
39. BIOLOGICAL FALSE POSITIVE(BFP) REACTIONS
As cardiolipin Ag is present both in T.Pallidum and in
mammalian tissues, reagin Abs may be induced by treponemal
or host tissue antigens which accounts for BIOLOGICAL FALSE
POSITIVE(BFP)
BFP defined as positive reactions obtained in cardiolipin tests,
with negative results in specific treponemal tests, in the absence
of past or present treponemal infections and not by technical
faults
They represent non-treponemal cardiolipin antibody responses
40. BFP Ab is usually IgM while Reagin Ab in syphilis is IgG
Represent non treponemal cardiolipin Ab responses
Clinically BFP reactions classified as acute & chronic
Acute BFP-last only for weeks or months, associated acute
infections, injuries or inflammatory conditions
Chronic BFP-persist longer than 6 months, seen in SLE & other
collagen diseases
Other conditions associated BFP reactions r leprosy, malaria, relapsing
fever, infectious mononucleosis, hepatitis & tropical eosinophilia
41. To avoid BFP reactions, tests using cultivable
treponemes(REITER STRAIN) as Ags were developed
Most common-Reiter Protein Complement Fixation(RPCF) using
lipopolysaccharide-protein complex Ag derived fron treponeme
Sensitivity & specificity- lower than tests using T. Pallidum
RPCF-generally free from BFP but gave false positive reactions
GROUP SPECIFIC TREPONEMAL TESTS
42. Specific test- Nichols strain
TPI-
Historical concept
Ability of Antibody + complement to immobilize
live T. pallidum visualized under darkground
microscope.
Flurescent treponemal antibody-
Indirect Immunofluorescence test using smears
prepared on slides with Nichols strain of T.Pallidum
43. FTA- Absorption- Patients serum first absorbed
with non pathogenic trep antigen ( sorbent ) to
remove low titer, natural cross reacting
antibodies
Difficult to standardize hence Particulate
agglutination test is preferred.
45. T.PALLIDUM HAEMAGGLUTINATION
ASSAY(TPHA)
Uses tanned ethrocytes sensitized with a sonicated extact of
T.Pallidum as Ag
Test sera for TPHA are absorbed with a diluent containing
components of the Reiter treponeme,rabbit testis & sheep
erythrocytes
Sera screened at initial dilution of 1:80 but titres of 5120 or
more-common in 2stage
TPHA-as specific as FTA-ABS, almost sensitive except in 1
These advantages have made TPHA-Standard Confirmatory
Test
46. FREQUENCY OF REACTIVE SEROLOGICAL TESTS IN UNTREATED SYPHILIS(%)
Stage VDRL/RPR FTA-ABS TPHA
Primary 70-80 85-100 65-85
Secondary 100 100 100
Latent/Late 60-70 95-100 95-100
48. Congenital syphilis
IgM immunoblotting- presence of IgM in
neonates confirm diagnosis.
Best way of monitoring is with serial
quantitative non treponemal tests.
Most reliable is test mother at time of birth
52. TREATMENT
Single inj. Of 2.4 million units of benzathine penicilliin G-adequate
in early cases
For latent syphilis-this amt repeated weekly for 3 wks
Pts allergic to penicillin-doxycyline used
Ceftriaxone-effective in neurosyphilis
Penicillin treatment sometimes induces-JARISCH-HERXHEIMER
REACTION-consisting of fever, malaise & exacerbation of
symptoms(due to liberation of toxic products like TNF from the
destruction of treponemes or due to hypersensitivity)
Harmless in 1 & 2 & managed bed rest & aspirin
Dangerous in gummatous,CV or neurosyphilis
53. Nonvenereal treponematoses
ENDEMIC SYPHILIS
Common in young children
Primary chancre is not seen, except sometimes on nipples of
mothers infected by their children
Usually seen with manifestation of secondary syphilis ,such as
mucous patches &skin eruptions
Disease progresses to tertiary lesions ,particularly gummatous
Lab diagnosis &treatment same as venereal syphilis
54. Yaws
Causative agent is T.pallidum subspecies pertenue
The primary lesion(mother jaw) is an extra genital papule
which enlarges & breaks down to form ulcerating granuloma
As in syphilis 2 & 3 manifestations follow
Destructive gummatous lesions of the bones are common
Infection by direct contact, flies may act as mechanical
vectors
Lab diagnosis & treatment are same as for venereal syphilis
55. PINTA
Causative agent is T.carateum
The primary lesion is an extra genital papule which
does not ulcerate but develops into a
lichenoid/psoriaform patch
Secondary skin lesions are charecterized by
hyperpigmentation/hypopigmentation
Tissues other than skin are seldom effected
Editor's Notes
First case 1905
John Hunters unfortunate self-inoculation with urethral pus containing both Neisseria gonorrhoeae and T. pallidum only served to prolong misconception s, because the two diseases were considered the same for some time thereafter. However, by the mid-19th century, the cause, epidemiology, and clinical manifestations of syphilis were well known
Outer membrane is lipid rich
This has led to the hypothesis that this microorganism acts as a stealth organism by minimizing the number of surface membranebound targets for the hosts immune system to recognize until a sufficient number of spirochetes are present.
The genome consists of a single circular chromosome of approximately 1,138,006 base pairs, which places it close to the lowest end of the range for bacteria. Unlike most pathogenic bacteria, its genome lacks apparent transposable elements, suggesting that the genome is extremely conserved and stable
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Unless secondarilyinfected, the ulcer has a clean appearance and no exudate; it is painless or slightly tender to the touch, a conspicuous aspect of the ulcerative
The secondary or disseminated stage becomes evident 2 to 12 weeks (mean, 6 weeks) after contact. This generalized condition with parenchymal, constitutional, and mucocutaneous manifestations occurs when the greatest number of treponemes (high antigen load) is present in the body, particularly in the bloodstream
The classic and most commonly recognized lesions involve the skin. Nonpruritic macular, maculopapular, papular, or pustular lesions, and combinations and variations thereof, all occur.
After the secondary stage subsides, the untreated patient enters a latent period, during which the diagnosis can be made only by obtaining a positive serologic test response for syphilis. Because relapses of secondary syphilis in immunocompetent persons can occur up to 4 years after contracting syphilis, this period is divided into early latent (relapses possible) and late latent (relapses very unlikely) stages; 75% of relapses occur within the frst year and are likely a consequence of waning immunity.
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Cardiovascular syphilis
Consist of lesions including aneurysms, chronic granulomata and meningovascular manifestation.
Gummatous syphis
Rare granulomatous lesion of skeleton, skin or mucocutaneous tissues.
Neurosyphilis
Neurological manifestation such as tabes dorsalis or general paralysis
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Direct diagnostic methods include the detection of T pallidum by microscopic examination of fluid or smears from lesions, histological examination of tissues or nucleic acid amplification methods such as polymerase chain reaction (PCR). Indirect diagnosis is based on serological tests for the detection of antibodies. Serological tests fall into two categories: nontreponemal tests for screening, and treponemal tests for confirmation