Syphilis

Question 1

Syphilis History:

• Define?
• Transmission?
• Origin?
• Synonyms?
• 21 Century?

Answer 1

• Syphilis: Is chronic potentially fatal infection of Treponema pallidum.
• Spread through sexual contact, IV drug abuse, Congenitally, contaminated blood products.
• The origin of syphilis:
  - Columbian theory (Christopher Columbus
  brought it back)
  - Pre-Columbian theory
  - Evolutionary theory (evolved from a pinta
  disease on skin to mucus membranes)
• Synonyms: The great pox, Morbus gallicus, , The great imitator.
• 21st century is the 5th leading STI in the uk.

Question 2

Spirochaetaceae: Treponema:

- Genus/species (2) and sub-species (3)?

Answer 2

Treponema carateum: causes pinta, spread by skin contact leading to skin lesions, scarring, disfigurement.

• Treponema pallidum
  Subspecies endemicum : causes Bejel transmitted by contaminated utensils leading to oral lesions.
• Treponema pallidum
  Subspecies: pertenue causes yaws transmitted by direct skin contact causes skin lesions destruction of lymph nodes and bone.
• Treponema pallidum
  sub-species: pallidum: causes syphilis transmitted by sexual/congenital causes primary- tertiary syphilis.

Question 3

Epidemiology:

• Reduction in? because of?
• Cases today? affect ages?
• why are cases increasing?

Answer 3

• Infection reduced in the 1940s with the advent of penicillin’s.
• Cases are increasing in current day and affects a wide range of age groups.
• Increases due to multifactorial changes in behaviors (alcohol, drugs, MSM), Associated with large outbreaks (the London outbreak in 2001-2004), Common behavioral characteristics of syphilis outbreaks (MSM)
• MSM high rate partner exchange, unprotected oral sex, social venues (internet, saunas), commercial sex workers.

Question 4

The natural history of untreated syphilis:

• Infective dose?
• Primary?
• Secondary?
• Tertiary?

Answer 4

• Infective dose 50-100
• Primary 3 weeks (10-90 days single painless ulcer (chancre) highly infectious. Wide spread dissemination throughout the body within hours of infection, many sites of infection, lymphadenopathy. Chancre often inconspicuous (MSM-rectum) heals spontaneously (2-6 weeks).
• Secondary: -18 weeks + Wide spread dissemination, symptoms appear approx 3months (6 weeks - 6months), Non-specific and specific presentation. Specific dissemination mucocutaneous rash, lymphadenopathy, alopecia (4-11%) condyloma lata (weird lumps).
• Tertiary syphilis: occurs 20-40 + years after initial exposure. Widespread progressive/chronic inflammation leading to gumma (nodular like lesions with necrotic center)(granulomatous lesions), cardiovascular syphilis, neurosyphilis (paresis, tabes dorsalis (syphilitic gait).

Question 5

Congenital syphilis: define:

• Early Onset symptoms?
• Late Onset symptoms?

Answer 5

• Congenital syphilis is the vertical transmission to the fetus.
• Early onset (2-10 weeks post birth) symptoms: Rhinitis (sniffles), skin lesions, +/- death (pulmonary hemorrhage/hepatitis).
• Late onset (>2 years)
• Hutchinson’s teeth (notched teeth)
• Saddle nose (looks like punched face).

Question 6

Causative micro-organism:

• organisms and morphology?
• size?
• Flagellum?
• Other things to note?

Answer 6

• Treponema: turning thread morphology.
• 0.1 um - 6.15 um cannot be gram stained!
• 3 Periplasmic flagellum (axial filaments/endoflagellum) corkscrew motility.

Other things to note:

• Limited metabolic capacity (usually absorbs sugars/fats etc from host).
• Unculturable on artificial medias
• Slow doubling time (30hrs)
• sensitive

Question 7

Virulence factors: Treponema pallidum ‘the perfect pathogen’.

• Virulence factors poorly understood.
• Attachment? proteins?
• Invasion?
• Motility?
• Chemotaxis?

Answer 7

• Attachment:
  
  • Gene Tp0155 - thought to encode from surface
    protein that binds to fibronectin
  • Gene Tp0483 - Thought to encode surface proteins
    that binds to matrix and soluble fibronectin.

Invasion:
- Hyaluronidase production = molecular mimicry of host hyaluronidase.

• Motility: corkscrew motion
• chemotaxis: MCP’s/Che proteins
  - Methyl-accepting chemotactic protein
  - Cytoplasmic chemotactic proteins.

Question 8

Diagnosis of syphilis:
Established through clinical observations and lab tests:

• Clinical diagnosis?
• Laboratory diagnosis?

Answer 8

• Clinical diagnosis is complicated because chancre are inconspicuous. The great imitator with non-specific symptoms.
• Laboratory diagnosis:
  • Confirm/Disprove clinical suspicion
  • Treponema: non-culturable on artificial media
  • Lab diagnosis established through: Direct microscopy, serological analysis.

Question 9

Dark ground microscopy:

• Clinical samples?
• What is dark ground microscopy?
• Interpretation of results?

Answer 9

Clinical samples:
- Exudate from penile chancre (primary) or condyloma lata (secondary)

Dark ground microscopy: light scatters away so makes a dark field when light hits organism it is reflected into the eye piece.

• Paraboloid condenser
• Light scattered by motile Treponemes
• Bright Treponemes against dark background, slow corkscrew like motility.

Results:

• Positive/ primary or secondary syphilis.
• Negative result does not rule out syphilis (>10^4 organisms are needed in excaudate.)

Question 10

Serological assay:

• What is it?
• looks for?
• Non specific and specific?

Answer 10

Serological assay looks for antibodies in patient serum against Treponemes or break down components associated with infection i.e phospholipids.

• Estimation of IgG and IgM antibodies.
• Non specific and specific antibodies produced in syphilis infection both exploited in serological assays.
• Non-specific (reagin) antibodies: Cardiolipin (phospholipid)/ Cholesterol.
• Specific antibodies: Flagellum proteins, surface lipids.

Question 11

Non-specific serological assay:

• VDLR testing?
• Tests for what?
• Positive result?
• Qualitative or quantitative?
• Use to monitor what?
• False positives?

Answer 11

• VDLR test: venereal disease reference lab
  
  • Excellent screening assay: detects non-specific (cardiolipin) antibody to cardiolipin/cholesterol/lecithin antigen (commercially available).
• Positive result = antibody flocculation
  
  • Sensitivity: primary (78%), secondary (100%), tertiary (71%).
• Qualitative and quantitative the latter utilizes serum dilutions.
• VDLR is used to monitor treat effectiveness.
• Biological false positive could be due to autoimmunity, connective issue disorders, viral infections, coronary artery disease.

Question 12

Specific Treponemal serological assay:

• TPHA?
• Results?
• Qualitative or quantitative?
• Sensitivity/specificity?

Answer 12

Treponemal pallidum haemoglutination assay:

• Treponeme pallidum antigen coated on RBC.
• Antibodies on serum = haemoglutination.
• Interpretation of results:
  
  • Haemoglutination = Positive
  • Buttoning of RBC = negative
• Qualitative and quantitative
• Sensitivity of 84%/ specificity 96%

Question 13

Specific serological assay:

• FTA-Abs?
• What is it?

Answer 13

Fluorescent Treponemal antibody absorption test.

• Acetone fixed T. pallidum (on glass slide)
• Incubated with patient serum
• Incubated with antihuman antibody conjugated with fluorescence (FITC labelled).
• Qualitative and quantitative.
• Sensitivity 84%

Question 14

Treatment:

• Historical?
• Current?
• Control of sphyilis?

Answer 14

• History:
  
  • Mercury fumigation, compound 606 (salvarsan)
  • 1945 penicillin

Current:

• syphilis <2 years: benzathine penicillin IM; oral doxycycline
• Syphilis >2 years: 3 x benzathine penicillin IM; oral doxycycline.

Control:

• Complicated 21st century lifestyle
• Screening for syphilis (pregnancy/gum clinics)
• Contact tracing and treatment
• no vaccine
• safe sex.