Syphillis

Question 1

What pathogen causes syphilis?

Answer 1

Treponema pallidum

Question 2

What type of pathogen is Treponema pallidum?

Answer 2

G –ve motile Spirochete

• Very sensitive to environmental stress
• Lacks many metabolic pathways - Amino acids, nucleotides, lipids
• Culture in cells possible
• Transmitted by prolonged sexual contact and abrasion - Needles and vertical possible
• Incubation period approx 3 weeks
• Closely related species cause pinta and yaws

Question 3

What are the stages of the pathogenesis of T. pallidum?

Answer 3

Primary Syphilis
Secondary (Disseminated) Syphyilis
Tertiary Syphilis
Congenital Syphilis

Question 4

Describe the pathogenesis of Primary syphilis

Answer 4

Results from the initial infection – chancre ulcer
- Site depends interaction – results in an ulcer
3 weeks – very slow growing
- Lesion disappears after a few weeks –
- lymphadenopathy for months
- Th1 response induced during infection

Question 5

Describe the pathogenesis of Secondary (disseminated) syphilis

Answer 5

2 – 8 weeks after chancre

• Generalised lymphadenopathy – mucocutaneous maculopapular rash – 2 – 6 weeks
  - Rash contains spirochetes – infectious hands
• Latency may occur – 3 -30 years – resolution possible

Question 6

Describe the pathogenesis of Tertiary syphilis

Answer 6

Outcome of disease depends on spread to cardiovascular or nervous system

• Gumma formation – skin bones testis
• Cardiosyphilis – colonisation of the vaso vasorum of aorta leading to necrosis – aneurisms
• Neurosyphilis – menigovasculitis, meningitis, fever, headache, mental changes – hallucinations and psychoses

Question 7

Describe the pathogenesis of Congenital syphilis

Answer 7

T. pallidum penetrates tight junctions of cells
Foetus may be infected – 4th month
Still born or changes to skeletal structure
Anaemia, thrombocytopenia and liver failure

Question 8

What proteins are involved in pathogenesis of T. pallidum? (7)

Answer 8

TP0155, TP0483, TP10136
TP0751
TPN47, TPN17, TPf1
TrpK

Question 9

How are TP0155, TP0483, and TP10136 involved in the pathogenesis of syphilis?

Answer 9

Binds the matrix and soluble forms of fibronectin, and o allows attachment and invasion of wounds

Question 10

How is TP0751 involved in the pathogenesis of syphilis?

Answer 10

Binds and degrades laminin and fibrinogen

• Zinc dependant membrane associated metaloprotease
• Promotes invasion - invasin
  - Access to blood stream and systemic spread
• Prevents clot formation
  - Access through wounds & Prevention of Containment

Question 11

How are TPN47, TPN17, and TPf1 involved in the pathogenesis of syphilis?

Answer 11

Immune avoidance- induction of IL10 and decoy of cells

Question 12

How is TrpK involved in the pathogenesis of syphilis?

Answer 12

Important in avoidance of the immune response

• TrpK is a target for immunity – opsinophagocytosis
• Protein is antigenically variable
• Variation begins as acquired immunity starts
• Variation occurs at transcriptional level
  - Transcribed from a variety of different sites on chromosome and combined - Segmental gene conversion
• Possibly key to establishment and maintenance of latency

Question 13

How is syphilis diagnosed?

Answer 13

Diagnosis is by serology or PCR
Serology is specific or non specific:
- Non specific - VDRL, RPR
- Specific - ElISA, FTA-ABS, MHA-TP

Question 14

How is syphilis treated?

Answer 14

Treatment is achieved with penicillin
Very little resistance – Banzathine penicillin G
Macrolide resistance occurs – azithromycin

Question 15

Can syphilis be prevented?

Answer 15

Vaccination is possible

• Gamma irradiated whole cells provide protection
• Other formulations only give partial protection
• Antigenic variation may be a problem

Question 16

Describe the treatment regimen for syphilis infection

Answer 16

The following regimens are recommended for penicillin treatment:
- Primary or secondary syphilis - Benzathine penicillin G 2.4 million units intramuscularly (IM) in a single dose

• Early latent syphilis - Benzathine penicillin G 2.4 million units IM in a single dose
• Late latent syphilis or latent syphilis of unknown duration - Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
• Pregnancy - Treatment appropriate to the stage of syphilis is recommended.