Lecture 8 Syphilis Flashcards

1
Q

What bacteria causes syphilis

A

Treponema pallidum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is syphilis the perfect pathogen

A

Spread vertically, mother to fetus, horizontally person to person and can hide in host for decades

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does s treponema spread

A

Through blood like Hep and HIV. Spread through sex, intravenous drugs and congenital (present from birth from mother)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name the three theories of syphilis origin and describe the notions

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why is it called the great imitator

A

Mocks the clinician as it mimicks lots of other clinical presentations of other diseases so hard to diagnose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name some famous syphilitics

A

Al capone, james Joyce

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In the C21st what position was syphilis ranked as concerning leading STIs in the UK

A

5th

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How many sub species of treponema pallidum are there and name them

A

3
Treponema pallidum subspecies. Pallidum (cause syphilis)
Treponema pallidum subspecies. Endemicum (cause Bejel disease)
Treponema pallidum subspecies. Pertenue (cause Yaws disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Are there any other treponema spp? If so name them

A

treponema carateum cause pinta disease - skin lesions, scarring and disfigurement from direct skin contact in central/south america

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What microorganism is the evolution theory of syphilis origin based on

A

Treponema carateum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is treponema pallidum subspecies endemicum spread

A

Through contaminated eating utensils (africa/asia) therefore get oral lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why has there been an increase in syphilis cases over the past decade across age groups

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When was the large london outbreak and how many infections were there

A

2001-2004

Approximately 1700 infections, 75% MSM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the timeline of primary to tertiary syphilis in weeks and years

A

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%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does primary syphilis involve

A
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is lymphadenopathy

A

Inflammation of lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Where doers a chancre occur

A

Point of contact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does treponema pallidum disseminate quickly through the body

A

Have surface hyaluronidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Are chancres painful? Why do they occur

A

No they are painless. Occur where treponema pallidum has burrowed through the tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the clinical manifestaitons of primary syphilis

A

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

21
Q

What are the characteristics of secondary syphilis

A

Widespread dissemination

Symptoms appear approximately 3 months (6weeks-6 months)
Non specific and specific presentation

22
Q

What are the symptoms of secondary syphilis

A

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

23
Q

When does tertiary syphilis occur

A

20-40years after initial exposure

24
Q

What are the symptoms of tertiary syphilis

A

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.

25
Q

How many phases does congenital syphilis occur in

A

2 phases

Early onset and late onset

26
Q

When does early onset congenital syphilis occur and what are the characteristics?

A

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

27
Q

When does late onset congenital syphilis occur and what are the characteristics?

A

> 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

28
Q

What is the structure and physiological properties of Treponema pallidum

A

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

29
Q

What virulence factors does Treponema pallidum have

A

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

30
Q

How is syphilis diagnosed

A

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

31
Q

What is the type of microscopy used for Treponema pallidum

A

Dark ground

32
Q

What clinical sample is used for syphilis

A

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

33
Q

How do Treponema pallidum look under dark ground microscopy and why

A

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.

34
Q

How many Treponema pallidum are needed approximately to see them via dark ground microscopy

A

10,000 in a sample.

If dont see one doesnt mean patient isnt positive.

35
Q

How do serological assays for Treponema pallidum work

A

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

36
Q

What clinical samples are used for SEROLOGICAL diagnosis

A

Serum most common = (clot blood and remove serum)
Cerebrospinal fluid (CSF) : neurosyphilis
Foetal cord blood : congenital syphilis in situ

37
Q

What is important to remember for safety handling suspected syphilitic sample

A

May have HIV or Hep B/C

38
Q

What is a non specific serological assay

A

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

39
Q

What is the sensitivity and specificity of non specific serological assay

A

Sensitivity: primary (78%), secondary (100%), tertiary (71%)
Specificity: 98%

40
Q

How is VDRL test used to monitor effectiveness of treatment

A

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.

41
Q

What is the issue with non specific antibody detection in VDRL

A

Can get false positives as other diseases such as viral, autoimmune, connective tissue disorders etc breakdown tissue

42
Q

What are the two types of SPECIFIC Treponemal serological asssays

A

TPHA (Treponema pallidum haemagglutination assay)

FTA-Abs (fluorescent treponemal antibody absorption test)

43
Q

What does the specific TPHA test consist of

A

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.

44
Q

What is thesensitivity and specificity of TPHA assay

A

Sens 84% spec 96%

45
Q

What is benefit of specific assays such as TPHA

A

Have specific antibodies for life. Unlike non specific

46
Q

What does the specific treponemal serological assay, FTA-Abs consist of

A

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)

47
Q

What treatment methods have been used historically for syphilis

A

Mercury fumigation, compound 606 (arsenic derivative)

48
Q

What is the current treatment regime for syphilis

A

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

49
Q

How can syphilis be controlled

A

Complicated due to 21st C lifestyle.
Screening for syphilis (pregnancy and gum clinics)

Contact tracing (difficult) and treatment

No vaccine so safe sex