Syphilis Flashcards
What is syphilis?
It is a chronic potentially fatal infection caused by Treponema pallidum
How is syphilis spread?
Intravenous drugs; congenita
What are the origins of syphilis?
•The origins of syphilis are controversial
(a) Columbian Theory (Christopher Columbus brought infection back from the Americas
(b) Pre-Columbian Theory (Hippocrates reported syphilis)
(c) Evolutionary Theory (Skin treponeme evolved to move from skin to mucous membranes as a result of cleansing)
What are the clinical manifestations of syphilis?
Syphilis has several synonyms:
- The Great Pox; Morbus gallicus;
- The Great Imitator
- Frequently portrayed in art / literature
- Famous syphilitics
Similar clinical presentation as other infections- called the ‘great imitator’
True or False: Syphilis is the 5th leading STI in UK (21st Century)
True
- What disease is caused by Treponema carateum?
- How is it spread?
- What are the clinical manifestations?
- Pinta.
- It is spread by direct skin contact (Centra-South America)
- Skin lesions, scarring, disfigurement
- What disease is caused by Treponema pallidum Subsp. endemicum?
- How is it spread?
- What are the clinical manifestations?
- Bejel
- Contaminated eating utensils (Africa/Asia)
- Oral lesions
- What disease is caused by Treponema pallidum Subsp. pertenue?
- How is it spread?
- What are the clinic
- Yaws
- Spread by direct skin contact (S.America/Africa/Asia
- Manifestations: Skin lesions, destruction of lymph nodes /bones
- What disease is caused by Treponema pallidum Subsp. pallidum**?
- How is it spread?
- What are the clinical manifestatioins?
- Syphilis
- Sexual/congenital (worldwide)
- Manifestations: Primary-tertiary syphilis
Describe the epidemiology of syphilis in the 21st century
•Reduction in late 1940s (introduction of penicillin)
- 2011: 2,900 (2002 - 2011: 87% increase)
- 2014: 4,317 (2011 -2014: 49% increase)
- 2015: 5,288 (2014 -2015: 22% increase)
What age groups are most affected by syphilis?
Wide range of age groups
What social and behavioural changes are related to the increased incidence of syphilis?
- alcohol, drugs, promiscuity, MSM
- MSM group
- high rate of partner change
- unprotected oral sex
- social venues / networks; internet; saunas; commercial sex workers (CSW) (esp. in heterosexual
True or False: Syphilis is associated with large outbreaks
True eg The ‘London Outbreak’ 2001-2004
70-80% in MSM community
Describe the natural history of untreated syphilis
- Infectious dose: 50-100
- 3 weeks after contact with the treponemal organism (10-90 days): single painless ulcer ‘__chancre’; highly infectious
- Widespread dissemination throughout the body within hours of infection
- Many sites of infection; lymphadenopathy
- Often inconspicuous (eg. MSM-rectum)
- Heal spontaneously (2-6 weeks)
What are the Clinical Manifestations and incubation period of Primary Syphilis?
- Incubation period: 10-90 days post contact
- Genital chancre (a painless open genital sore usually on penis or vagina, mouth or anus; sometimes inside vagina or on cervix)
- Lymphadenopathy
- Spontaneous healing (2-6 weeks)
Describe the the natural history of untreated syphilis (secondary)
Widespread dissemination
Symptoms appear approx 3 months (6 weeks- 6 months)
Non specific and specific presentation
Specific: disseminated mucocutaneous rash; alopecia; condyloma lata (highly infectious, contains lots of treponema pallidum wart-like structures)
What are the Clinical Manifestations and incubation period of Secondary Syphilis?
•Incubation period: 6 weeks - 6 months post contact
- Non-specific (difficult to diagnose syphilius)
- Specific symptoms
(a) Mucocutaneous rash (inflammatory response to widespread treponemal antigens)
(b) Lymphadenopathy
(c) Alopecia
(d) Condyloma lata
Describe the natural history of untreated syphilis (tertiary)
20- 40 years after initial exposure
Widespread progressive / chronic inflammation leading to:
- Gumma (nodular-like lesions in skin, bone, heart CNS)
- Cardiovascular syphilis
- Neurosyphilis (paresis, tabes dorsalis)
What are the Clinical Manifestations and incubation period of tertiary Syphilis?
Most destructive form of syphilis
- Occurs months / years after initial contact
- Most destructive form of syphilis (skin, tissues, eyes, bone, brain, heart)
- Granulomatous lesions (Gumma’s)
- Cardiovascular syphilis
(10 -30 years after initial infection)
•Neurosyphilis (hallucination, confusion, etc)
- Paresis
- Tabes dorsalis
What are the clinical manifestations of early onset Congenital Syphilis?
Early onset (2-10 weeks post-delivery)
- Sniffles (rhinitis due to the organisms hight affinity for nasal cartilage)
- Skin lesions
- +/- death (pulmonary haemorrhage / hepatitis)
What are the clinical manifestations of late onset Congenital Syphilis?
Late onset (> 2 years)
- Hutchinson’s teeth
- Saddle nose
Describe the physiology and structure of Treponema pallidum
Treponema: ‘Turning thread’
- 0.1µm x 6-15µm•
- 3 periplasmic flagella (axial filaments / endoflagella); corkscrew motility
- Limited metabolic capacity
Cannot stain the organism
- Uncultureable on artificial media (cannot be grown on blood agar)
- Slow doubling time (about 30 hours)
- Sensitive (e.g. doesn’t like dry environments)
Virulence Factors of Treponema pallidum: What promotes attachment?
- Tp0155 is a surface protein which binds to matrix fibronectin
- Tp0483 is a surface protein which binds to both matrix and soluble fibronectin (form of molecular mimicry- difficult for host to differentiate between organism and self)
Virulence Factors of Treponema pallidum: What promotes Invasion?
Hyaluronidase production (degrade extracellular matrix) / molecular mimicry
Virulence Factors of Treponema pallidum: Describe its Motility?
corkscrew motion
Virulence Factors of Treponema pallidum: What promotes Chemotaxis?
- (MCs / Che protein
- methyl-accepting chemotactic proteins
- cytoplasmic chemotactic proteins
Move toward more favourable conditions
How is syphilis diagnosed?
Established through clinical observations and laboratory tests
Why is the clinical diagnosis of syphilis complicated?
•Clinical Diagnosis: complicated
(a) Chancre often inconspicuous
(b) Syphilis – ‘the great imitator’
Describe the laboratory diagnosis of syphilis
•Laboratory Diagnosis
(a) Confirms / disprove clinical suspicion
(b) Treponema: non-culturable on artificial media-Can’t grow the organism so non-culture techniques used
(c) Laboratory diagnosis established through:
- Direct microscopy (can’t use Gram stain for direct microscopy)
-Serological assays
Diagnosis of syphilis: Dark-Ground Microscopy
What clinical samples are required?
(a) Exudate from penile chancre (primary)or condyloma lata (secondary).
Diagnosis of syphilis: Describe Dark-Ground Microscopy
(a) DGM: Paraboloid condenser
(b) Light scattered (into eyepiece) by motile treponemes if present
(c) Bright treponemes against a dark background; slow, corkscrew-like motility
How are results of dark ground microscopy interpreted?
(a) Positive result: primary / secondary syphilis
(b) Negative result: does not rule out syphilis (≥ 104 treponemes are needed in exudate)
Diagnosis of syphilis: Serological Assays
- Estimation of IgM / IgG antibodies
- Non-specific and specific antibodies produced in syphilis infection – both exploited in serological diagnosis
Serological assays: Non-specific (reagin) antibodies:
CARDIOLIPIN (PHOSPHOLIPID) / CHOLESTEROL
Serological assays: S_pecific (reagin) antibodies_:
Against treponema pallidum e.g Flagella proteins, surface lipids
Which clinical samples are required for serological diagnosis
(A) Serum
(B) Cerebrospinal fluid (CSF): if neurosyphilis suspected
(C) Fetal cord blood: if congenital syphilis suspected
State some Safety Issues
(Hep B/C, HIV)
Diagnosis: Non-Specific Serological Assay
VDRL Test (venereal disease reference laboratory)
- Excellent ‘screening’ assay: Detects non-specific (cardiolipin) antibody to cardiolipin / cholesterol / lecithin antigen (commercially available)
- +ve result: antigen flocculation (antibody combines with cholesterol phospholipid)
Sensitivity: primary (78%); secondary (100%); tertiary (71%)
Specificity: 98%
- Qualitative / Quantitative
- VDRL used to monitor the effectiveness of treatment:
(a) T. pallidum uncultureable
(b) no agar sensitivity test available
•Biological false positives (BFPs): autoimmune disease, connective tissue disorders, viral infection, coronary artery disease…..
If VDRL antibody titer goes doe e.g. from 1:16 to 1:2 then the antibiotic is working. Important because antibody sensitivity testing cannot be performed.
Diagnosis: specific Treponemal Serological Assays
.TPHA (Treponema pallidum Haemagglutination Assay
- Treponema pallidum antigen coated onto RBC
- Antibodies in serum=haemagglutination of RBC
- Interpretation of results:
(a) Haemagglutination = +ve(b)Buttoning of RBC = -ve
- Qualitative / Quantitative
- Sensitivity: 84% / Specificity 96%
Describe specific Treponemal Serological Assays
FTA-Abs (fluorescent treponemal antibody absorption test
- Acetone fixed T. pallidum (on glass slides)
- Incubated with patients serum
- Incubated with anti-human antibody conjugate (FITC labelled)
- Qualitative / quantitative
- Sens 84% / spec 97%
Describe the history of Syphilis Treatment
- Mercury fumigation, compound 606 (arsenic based) (salvarsan)
- 1945: Penicillin
- 21st Century:
- syphilis < If condition is less than 2 years of progression: benzathine penicillin IM single dose; oral doxycycline 10-14 days
- syphilis > 2years: 3 X benzathine penicillin IM single dose; oral doxycycline 28 days
Describe the Control of syphilis:
- Complicated: 21st century lifestyle
- Screening for syphilis (pregnancy / GUM clinics)
- Contact tracing and treatment
- No vaccine; safe sex
Syphilis: key points
•Chronic, potentially fatal STI –with history
- Transmitted sexually, intravenous drugs, congenital route
- Primary, secondary, tertiary stages
- Treponema pallidum: genome sequenced; limited virulence factors••Diagnosis: clinical; microscopy and serological assays
- UK Treatment: I.M procaine benzylpenicillin
- Control: safe sex
