Lecture 8 Syphilis Flashcards
What bacteria causes syphilis
Treponema pallidum
Why is syphilis the perfect pathogen
Spread vertically, mother to fetus, horizontally person to person and can hide in host for decades
How does s treponema spread
Through blood like Hep and HIV. Spread through sex, intravenous drugs and congenital (present from birth from mother)
Name the three theories of syphilis origin and describe the notions
Colombian theory - christopher Columbus travelled to americas and came back, great pox spread across Europe - presumed brought back.
Pre-Colombian theory - around before he travelled to america - most likely as description by hippocrates something like syphilis
Evolution - unlikely, treponema skin bacteria and with cleaning practices evolved to survive
Why is it called the great imitator
Mocks the clinician as it mimicks lots of other clinical presentations of other diseases so hard to diagnose
Name some famous syphilitics
Al capone, james Joyce
In the C21st what position was syphilis ranked as concerning leading STIs in the UK
5th
How many sub species of treponema pallidum are there and name them
3
Treponema pallidum subspecies. Pallidum (cause syphilis)
Treponema pallidum subspecies. Endemicum (cause Bejel disease)
Treponema pallidum subspecies. Pertenue (cause Yaws disease)
Are there any other treponema spp? If so name them
treponema carateum cause pinta disease - skin lesions, scarring and disfigurement from direct skin contact in central/south america
What microorganism is the evolution theory of syphilis origin based on
Treponema carateum
How is treponema pallidum subspecies endemicum spread
Through contaminated eating utensils (africa/asia) therefore get oral lesions
Why has there been an increase in syphilis cases over the past decade across age groups
Behavioural changes such as drugs/promiscuity
MSM group - higher rate of partner change, unprotected oral sex ,
Commercial sex workers in heterosexuals, also for both sexualities: social venues/internet grindr etc
When was the large london outbreak and how many infections were there
2001-2004
Approximately 1700 infections, 75% MSM
Describe the timeline of primary to tertiary syphilis in weeks and years
Primary 0-8 weeks then become asymptomatic for approx 10 weeks.
Secondary week 18/19-25 then LATENCY and asymptomatic
May reactivate after approximately 12 years as tertiary (30%) or may get no further complications (70%)
What does primary syphilis involve
Infection of dose approx 50-100 (very low) 3 weeks (10-90 days) single painless chancre (ulcer) which is highly infectious . Often inconspicuous (e.g. MSM-rectum) , heal spontaneously 2-6 weeks.
Widespread dissemination in the body within hours of infection
Many sites of infection (lymphadenopathy)
What is lymphadenopathy
Inflammation of lymph nodes
Where doers a chancre occur
Point of contact
How does treponema pallidum disseminate quickly through the body
Have surface hyaluronidase
Are chancres painful? Why do they occur
No they are painless. Occur where treponema pallidum has burrowed through the tissue
What are the clinical manifestaitons of primary syphilis
Incubation period 10-90days
Genital chancre - normally, on penis, vagina, mouth or anus sometimes inside vagina or on cervix
Lymphadenopathy
Spontaneous healing of chancre 2-6 weeks
What are the characteristics of secondary syphilis
Widespread dissemination
Symptoms appear approximately 3 months (6weeks-6 months)
Non specific and specific presentation
What are the symptoms of secondary syphilis
Specific: Disseminated mucocutaneous rash (red blotches over skin), lymphadenopathy, alopecia (4-11% of patients), condyloma lata (wart structures on hands which are extremely infectious!!)
Non specific symptoms
When does tertiary syphilis occur
20-40years after initial exposure
What are the symptoms of tertiary syphilis
Most destructive form affect skin, tissues, eyes, bone, brain and heart.
GUMMA - granulomatous regions - lesions with necrotic centre on skin, bone or heart.
Cardiovascular syphilis - organisms reside in heart and can get inflammation around the heart, may present with aortic aneurysms
Neurosyphilis (affect nervous system). Can get Paresis (depression, hallucinations, seizures) and tabes dorsalis (affect dorsal part of spine so have syphilitic gate, drag feet as walk from CNS infection.
How many phases does congenital syphilis occur in
2 phases
Early onset and late onset
When does early onset congenital syphilis occur and what are the characteristics?
2-10 weeks post delivery
Sniffles (rhinitis) - as t pallidum has high affinity for bone and nasal cartilage
Skin lesions - like rash of secondary syphilis
+/- death (pulmonary haemorrhage / hepatitis
When does late onset congenital syphilis occur and what are the characteristics?
> 2 years if survive early onset.
Hutchinsons teeth - notches in the teeth
Saddle nose - not fully formed due to t. Pallidum high affinity for nasal cartilage
What is the structure and physiological properties of Treponema pallidum
Spirochete - move like a corkscrew.
3 periplasmic flagella (endoflagella) - go from one of organism to the other which helps them flex like a corkscrew
Limited metabolic capability - dont have krebs cycle - tend to get energy from us which absorb through outer layers from the host (reason why we cant grow on blood agar)
30 hrs doubling time
Sensitive to dry environment and environmental extremes (including antibiotics) therefore cant live outside human host for very long
What virulence factors does Treponema pallidum have
Attachment
TP0155- bind to matrix fibronectin
Tp0483 bind to matrix and soluble fibronectin (mask itself in host fibronectin as molecular mimicry)
Invasion: hyaluronidase production and molecular mimicry
Motility: burrow through gelatinous inflammatory material using corkscrew motion
Chemotaxis: MCPs and Che proteins (move to areas with nutrition and avoid unfavourable environments
(Methyl-accepting chemotactic proteins and cytoplasmic chemotactic proteins
How is syphilis diagnosed
Clinical - chancre, rash possibly but difficult to diagnose clinically!!
Lab - confirm/disprove suspicion of clinician. Treponema not culturable on artificial media, therefore need to use
DIRECT MICROSCOPY AND SEROLOGICAL ASSAYS
What is the type of microscopy used for Treponema pallidum
Dark ground
What clinical sample is used for syphilis
Excudate from penile chancre (primary) or condyloma Lara (secondary)
Taken with moistened gauze and sterile water and rubbed a bit of chancre to get liquid which is put on microscope slide
How do Treponema pallidum look under dark ground microscopy and why
Bright treponemes against dark background (slow corkscrewlike motility)
Paraboloid condenser - when light goes through the light is scattered away from objective hence dark background. Light is scattered by the mobile treponemes therefore they reflect light into the objective so appear very bright.
How many Treponema pallidum are needed approximately to see them via dark ground microscopy
10,000 in a sample.
If dont see one doesnt mean patient isnt positive.
How do serological assays for Treponema pallidum work
Estimation of IgM and IgG antibodies
Non specific and specific antibodies produced - both used here.
Non specific antibodies - see these in common cold too, respond to phospholipid (cardiolipin) and cholesterol in blood stream from destruction of host cells .
Specific - against flagella proteins or surface lipids
What clinical samples are used for SEROLOGICAL diagnosis
Serum most common = (clot blood and remove serum)
Cerebrospinal fluid (CSF) : neurosyphilis
Foetal cord blood : congenital syphilis in situ
What is important to remember for safety handling suspected syphilitic sample
May have HIV or Hep B/C
What is a non specific serological assay
Venereal disease reference laboratory (VDRL Test)
Add patient sample to antigen and if get flocculation then positive test.
Excellent screening assay - detects non specific antibody to cardiolipin/cholesterol/lecithin antigen (commercially available) as a positive control
Positive result is antigen flocculation
What is the sensitivity and specificity of non specific serological assay
Sensitivity: primary (78%), secondary (100%), tertiary (71%)
Specificity: 98%
How is VDRL test used to monitor effectiveness of treatment
Can dilute serum normally in doubling dilutions to get an antibody titre. Keep diluting until get last one to get growth as dilution.
Cant do sensitivity testing on it as cant grow on agarose.
What is the issue with non specific antibody detection in VDRL
Can get false positives as other diseases such as viral, autoimmune, connective tissue disorders etc breakdown tissue
What are the two types of SPECIFIC Treponemal serological asssays
TPHA (Treponema pallidum haemagglutination assay)
FTA-Abs (fluorescent treponemal antibody absorption test)
What does the specific TPHA test consist of
Coat RBC with Treponema pallidum antigen . Mix patients serum with RBC and if antibody is present get haemaggultination. If not get a button at the bottom of the well.
What is thesensitivity and specificity of TPHA assay
Sens 84% spec 96%
What is benefit of specific assays such as TPHA
Have specific antibodies for life. Unlike non specific
What does the specific treponemal serological assay, FTA-Abs consist of
Buy in commercial treponema antigen and fix it to slide using acetone. Incubate with patients serum and then add anti-human antibody conjugate labeled with FITC.
Indirect form of immunofluorescence assay and if patient have antibody get green flow (identify the microorganisms)
What treatment methods have been used historically for syphilis
Mercury fumigation, compound 606 (arsenic derivative)
What is the current treatment regime for syphilis
Syphilis < 2 years : benzathine penicillin Intramuscular as a single dose, oral doxycycline 10-14 days
Syphilis >2 years: 3 x benzathine penicillin IM, oral doxycycline for 28 days.
Doxycycline is used if cant take penicillin for allergies. Benzathine makes the penicillin slow release
How can syphilis be controlled
Complicated due to 21st C lifestyle.
Screening for syphilis (pregnancy and gum clinics)
Contact tracing (difficult) and treatment
No vaccine so safe sex
