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2021-22 Clinical microbiology > Syphilis > Flashcards

Syphilis Flashcards

1
Q

What is syphilis?

A

It is a chronic potentially fatal infection caused by Treponema pallidum

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2
Q

How is syphilis spread?

A

Intravenous drugs; congenita

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3
Q

What are the origins of syphilis?

A

•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)

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4
Q

What are the clinical manifestations of syphilis?

A

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’

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5
Q

True or False: Syphilis is the 5th leading STI in UK (21st Century)

A

True

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6
Q
  1. What disease is caused by Treponema carateum?
  2. How is it spread?
  3. What are the clinical manifestations?
A
  1. Pinta.
  2. It is spread by direct skin contact (Centra-South America)
  3. Skin lesions, scarring, disfigurement
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7
Q
  1. What disease is caused by Treponema pallidum Subsp. endemicum?
  2. How is it spread?
  3. What are the clinical manifestations?
A
  1. Bejel
  2. Contaminated eating utensils (Africa/Asia)
  3. Oral lesions
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8
Q
  1. What disease is caused by Treponema pallidum Subsp. pertenue?
  2. How is it spread?
  3. What are the clinic
A
  1. Yaws
  2. Spread by direct skin contact (S.America/Africa/Asia
  3. Manifestations: Skin lesions, destruction of lymph nodes /bones
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9
Q
  1. What disease is caused by Treponema pallidum Subsp. pallidum**?
  2. How is it spread?
  3. What are the clinical manifestatioins?
A
  1. Syphilis
  2. Sexual/congenital (worldwide)
  3. Manifestations: Primary-tertiary syphilis
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10
Q

Describe the epidemiology of syphilis in the 21st century

A

•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)
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11
Q

What age groups are most affected by syphilis?

A

Wide range of age groups

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12
Q

What social and behavioural changes are related to the increased incidence of syphilis?

A
  • 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
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13
Q

True or False: Syphilis is associated with large outbreaks

A

True eg The ‘London Outbreak’ 2001-2004

70-80% in MSM community

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14
Q

Describe the natural history of untreated syphilis

A
  • 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)
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15
Q

What are the Clinical Manifestations and incubation period of Primary Syphilis?

A
  • 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)
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16
Q

Describe the the natural history of untreated syphilis (secondary)

A

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)

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17
Q

What are the Clinical Manifestations and incubation period of Secondary Syphilis?

A

•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

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18
Q

Describe the natural history of untreated syphilis (tertiary)

A

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)
19
Q

What are the Clinical Manifestations and incubation period of tertiary Syphilis?

A

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
20
Q

What are the clinical manifestations of early onset Congenital Syphilis?

A

Early onset (2-10 weeks post-delivery)

  • Sniffles (rhinitis due to the organisms hight affinity for nasal cartilage)
  • Skin lesions
  • +/- death (pulmonary haemorrhage / hepatitis)
21
Q

What are the clinical manifestations of late onset Congenital Syphilis?

A

Late onset (> 2 years)

  • Hutchinson’s teeth
  • Saddle nose
22
Q

Describe the physiology and structure of Treponema pallidum

A

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)
23
Q

Virulence Factors of Treponema pallidum: What promotes attachment?

A
  • 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)
24
Q

Virulence Factors of Treponema pallidum: What promotes Invasion?

A

Hyaluronidase production (degrade extracellular matrix) / molecular mimicry

25
Virulence Factors of *Treponema pallidum:* Describe its **Motility**?
corkscrew motion
26
Virulence Factors of *Treponema pallidum:* What promotes **Chemotaxis**?
* (MCs / Che protein * methyl-accepting chemotactic proteins * cytoplasmic chemotactic proteins Move toward more favourable conditions
27
How is syphilis diagnosed?
Established through _clinical observations_ and _laboratory tests_
28
Why is the clinical diagnosis of syphilis complicated?
•Clinical Diagnosis: complicated (a) Chancre often inconspicuous (b) Syphilis – *‘the great imitator’*
29
Describe the laboratory diagnosis of syphilis
•Laboratory Diagnosis ## Footnote (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***
30
Diagnosis of syphilis: Dark-Ground Microscopy What clinical samples are required?
(a) Exudate from penile chancre (primary)or condyloma lata (secondary).
31
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
32
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)
33
Diagnosis of syphilis: Serological Assays
* Estimation of IgM / IgG antibodies * Non-specific and specific antibodies produced in syphilis infection – _both exploited in serological diagnosis_
34
Serological assays: **_Non-specific (reagin) antibodies_**:
CARDIOLIPIN (PHOSPHOLIPID) / CHOLESTEROL
35
Serological assays: **S_pecific (reagin) antibodies_**:
Against *treponema pallidum* e.g Flagella proteins, surface lipids
36
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
37
State some Safety Issues
(Hep B/C, HIV)
38
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.
39
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%
40
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%
41
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
42
Describe the Control of syphilis:
* Complicated: 21st century lifestyle * Screening for syphilis (pregnancy / GUM clinics) * Contact tracing and treatment * No vaccine; safe sex
43
Syphilis: key points
•Chronic, potentially fatal STI –with history ## Footnote * 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

2021-22 Clinical microbiology (10 decks)

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