ERS36 Sexually Transmitted Disease Flashcards

1
Q

STI

A

Definition: Disease transmitted by sexual contact

HIV, Syphilis may also be transmitted by blood transfusion / needle stick injury
- do not “travel alone” (may have >1 STD)
- many asymptomatic (act as reservoir for ongoing transmission)

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2
Q

Encounter + Entry of STI agents

A
  • NOT survive in environment (very sensitive to drying, disinfectant, heat)
  • NOT free-living —> Practically never found free in environment
  • NO animal reservoir
    —> cannot blame toilet seat / bath tub

Entry:
- Reservoir: asymptomatic human carrier (human-to-human transmission)
- Mucous membrane (Columnar epithelium) / Minute abrasions on skin (Squamous epithelium)
- Local sites (vagina, cervix, urethra, rectum, pharynx)
- Primary lesions at / near site of entry

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3
Q

Consequence / Complications of STI

A
  1. ***Pelvic inflammatory disease
    —> infertility, ectopic pregnancy
  2. Anogenital cancer (predisposed by HPV infection)
  3. Secondary / Tertiary syphilis
  4. Recurrent herpes infection
  5. Increase risk of HIV infection
  6. Adverse outcome of pregnancy
  7. Congenital diseases (e.g. Syphilis, Herpes) —> can be life-threatening to baby
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4
Q

Major STI in HK

A

Decreasing incidence:
1. Chlamydia trachomatis
- Non-gonococcal urethritis (NGU) —> Male
- Non-specific genital infection (NSGI) —> Female
2. Genital warts
3. Gonorrhoea
4. Syphilis
5. Genital herpes

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5
Q

***Clinical presentations of STD

A

Big 3:
1. Urethral discharge (Urethritis: Male)
2. Genital ulcer (Male / Female)
3. Genital lumps (Male / Female)

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6
Q
  1. Urethral discharge
A

Caused by Urethritis

Main causes:
1. **Neisseria gonorrhoea (GC) (淋病雙球菌)
2. **
Chlamydia trachomatis (CT) (衣原體)

Other organisms (controversial) —> NOT generally work-up
3. Mycoplasma genitalium
4. Ureaplasma urealyticum
5. HSV (rare)
6. Trichomonas vaginalis (rare)
7. Yeasts (rare)

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7
Q

***Typical urethritis

A
  1. Gonorrhoea Urethritis (GU) (淋病/白濁)
    - Neisseria gonorrhoeae: Gram -ve diplococci
    - 2-5 days incubation
    - **Abrupt onset
    - **
    Prominent dysuria
    - ***Copious, Milky discharge
    - Rare relapse
  2. Non-gonococcal urethritis (NGU) —> Chlamydia trachomatis
    - 7-14 days incubation
    - **Gradual onset
    - **
    Mild dysuria
    - ***Little discharge
    - Common relapse
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8
Q

Management of urethritis

A
  1. Establish presence of urethritis
    - P/E + Microscopy (WBC, Bacteria)
  2. 2 approaches of treatment
    - 1. **Empirical treatment —> No work up in initial visit —> **cover both GC + CT
    - 2. Work up and treat
    —> depends on availability of tests, patients’ preference
  3. Evaluate + Treat partner appropriately
  4. Follow-up examination (optional)
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9
Q

Drug treatment for urethritis

A

Cover for both GC + CT:
**Ceftriaxone (single dose IM for **GC) + **Azithromycin (single dose for **CT) / Doxycycline (7 days for CT)

Tetracycline, Penicillin, Fluoroquinolone, oral Cephalosporin
—> Abandoned as 1st line for GC (∵ resistance common)
—> unless have culture / susceptibility results

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10
Q

Chlamydial infections

A

Family: Chlamydiaceae
Genus: Chlamydia

Obligate **Intracellular parasite
1. Chlamydia trachomatis
- A, B, C —> Trachoma (eye disease)
- **
D to K —> Cervicitis, Urethritis, PID, Neonatal pneumonia
- ***L —> Lymphogranuloma venereum (LGV) (LN infection)

  1. Chlamydia pneumoniae —> Respiratory tract infection
  2. Chlamydia psittaci —> Psittacosis (respiratory tract)
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11
Q

Collection of sample from Penis, Anal canal, Cervix

A

Penis:
Insert specimen swab 0.5 - 1cm into urethra
—> rotate several times within urethra
—> transport in transport jelly
—> send for bacterial culture

Anal canal / Cervix:
Use larger specimen swabs

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12
Q

***2 swabs

A

1st one for GC culture, 2nd one for CT culture

  1. GC culture
    - GC dies quickly
    - **directly inoculate into agar palate at bedside (preferred)
    - Transport specimen in special transport tube / swab —> send to lab **
    IMMEDIATELY (any delay compromise yield)
    - ***Never refrigerate specimen

Main test: Culture
- Must use nutritive culture media with antibiotics (to inhibit overgrowth of normal flora) (selective / differential medium)
—> Modified Thayer-Martin medium (exam: Selective medium for Neisseria gonorrhoeae) —> small, greyish-white to colour mucoid colonies
—> ***Martin-Lewis medium
- 35oC, CO2 enriched, humid

  1. CT culture
    - transport and storage requirement completely different
    - specimen **MUST be sent in special transport medium (X swab)
    - **
    can be refrigerated (4oC) for up to 24 hrs if cannot deliver to lab immediately
  • 2 methods
    —> **Cell culture (e.g. **McCoy cell line) (∵ obligatory intracellular organism) —> **Cytopathic changes with **Inclusion bodies inside McCoy cells

—> Antigen detection (e.g. Chlamydiazyme)
- perform directly on clinical specimen
- rapid test result
- less sensitive than culture
- false positive results from cross reacting bacterial species

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13
Q

Pharyngeal gonorrhoea

A

AIDS / Immunocompromised: Gonococcal pharyngitis
Immunocompetent: Asymptomatic —> diagnostic difficulty

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14
Q

Alternative work-up approach

A

***Nucleic acid amplification tests (NAAR)
- PCR
- LCR (Ligase chain reaction)
- TMA (Transcription-mediated amplification)

Advantages:
- **Faster (~ hours) (∵ culture take a few days)
- **
Detect both GC + CT in one specimen
- ***Higher sensitivity than culture —> reliable
- Can be performed on non-invasive specimens (e.g. urine, vulval swab) with good results
—> make screening people at risk acceptable

Limitations:
- ***Costs

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15
Q
  1. Genital ulcer (Male / Female)
A
  • Single / Multiple
  • With / without vesicles
  • Different forms
  1. ***Syphilis (梅毒)
  2. ***Herpes simplex (生殖器疱疹)
  3. Chancroid (軟性下疳)

(4. Lymphogranuloma venereum LGV (rare)
5. Donovanosis (rare): by Calymmatobacterium granulomatis)

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16
Q

Syphilis vs Herpes vs Chancroid vs LGV vs Donovanosis

A

Syphilis:
- **Clean base
- **
Indurated (Hardened) elevated edge
- Not tender (Chancres)

Chancroid:
- **Dirty, gray base
- Soft edge
- **
Marked tenderness

Herpes:
- **Multiple shallow ulcerations + vesicles
- **
Erythematous rim

Donovanosis:
- ***Beefy red base
- Elevated
- Serpiginous (wavy) edge

LGV:
- ***Prominent lymphadenopathy / enlarged inguinal LN

(see table for more details)

17
Q

Approach for genital ulcerations

A

If Typical syndrome
—> Lab tests may not be necessary

If Lab service limited
—> syndromic management approach may be used

18
Q

***Genital herpes

A

Causative agent:
Herpes simplex viruses
- type 1 (10%): mouth
- ***type 2 (90%): genital strain

Gross:
***Ulcerating vesicles

Incubation period:
- 2-5 days

Diagnosis:
- based on clinical appearance

Laboratory diagnosis:
1. **Tzanck smear
- only positive in ~50% of cases
- smear obtained by scraping base of vesicle / ulcer with a scalpel
—> material then fixed in alcohol
—> stained with **
Wright / Giemsa stain
—> ***Multinucleated giant cells (characteristic of Herpes infection (not necessarily simplex))

  1. ***Viral culture
    - days
    - positive up to 80% (depend on stage)
    - Cytopathic effect in cell line (A549 cell)
  2. Antibody test
    - no use in diagnosis
19
Q

Herpes infection

A
  • Can recur despite treatment
  • **NO antiviral can eliminate latency in neurons
    —> can **
    only treat active lesions
    —> cannot prevent reactivation

Mucocutaneous infection
—> Spread to local sensory nerve endings
—> Establishment + Maintenance of neuronal latency in ***ganglion
—> Reactivation of virus + distal spread
—> Mucocutaneous infection recurrence

20
Q

***Syphilis

A

Causative agent:
**Treponema pallidum (a **spirochete 螺旋體)
- helical
- slender
- long cells
- flagella within periplasm

***NOT cultivable in artificial media

Pathogenesis:
- ***Multiply very slowly —> Long incubation period
- Enter body through minute abrasions

Primary syphilis —> ***local multiplication —> Ulceration (Chancre) / inflammation —> Healing spontaneously

Secondary syphilis —> **Bloodstream dissemination —> Organism localised around blood vessels —> **Lesions in skin, mucous membrane, LN, CNS etc. —> later ***Endarteritis (inflammation of the inner lining of an artery)

Latent syphilis —> Residual organism in ***Spleen / LN

Late syphilis —> Renewed multiplication of Residual organism —> take many years before patient present clinically —> ***damage to organ / tissue

21
Q

Natural history of Syphilis

A

***Infectivity ↓ rapidly with time (< 2 years highly infectious, > 2 years less infectious) —> 用2年做分界線

Early Syphilis (***< 2 years):
Infection (incubation period: 9-90 days)
—> Primary
(6 weeks-6 months)
—> Secondary
—> Early latent

Late Syphilis (***> 2 years):
(3-30 years)
—> Late latent
—> Spontaneous cure / Persistent latent / Tertiary syphilis (each 33%)

22
Q

***Microbiological diagnosis of Syphilis

A
  1. **Serology
    - Specific Ab detection
    - **
    Mainstay approach
  2. Direct microscopy of ulcer exudate
    - NOT sensitive
    —> **Dark field microscopy (very tiny organism, 5-20 regular spirals rotation, undulation, compression, expansion)
    —> Immunofluorescence staining (not generally available)
    —> **
    Cannot be visualised by Gram stain!!!
23
Q

***Serological diagnosis of Syphilis

A

Often take **>= 2-4 weeks for result to be positive (even weeks after initial symptoms)
—> **
take long time for Ab to develop
—> Ab may still be lower than detection limit even symptoms appear

Non-treponemal specific tests (***L/R字尾)
1. VDRL test (venereal disease research laboratory)
2. RPR test (rapid plasma reagin)

Advantages:
- distinguish **Past / Inactive vs Untreated syphilis (∵ Ab level之後會降低)
- expressed in titre —> **
Disease activity indicator

Disadvantages:
- Biological false-positive

Treponemal specific tests (***A字尾)
1. EIA-syphilis test (enzyme immunoassay)
2. TPPA test (treponema pallidum particle agglutination assay)
3. FTA-abs test (fluorescent treponemal antibody absorption)

Advantages:
- ***More specific

Disadvantage:
- unable to distinguish ***Past syphilis (treated) vs Untreated syphilis —> result remain positive for life (∵ Ab level唔會降低)

***Overall: Use combination of both Non-treponemal + Treponemal specific tests
—> Tests results also MUST be interpreted with patient history (∵ may have false-positive)

24
Q

Traditional screening algorithm

A

Non-treponemal specific test (e.g. RPR)
—> Reactive —> Treponemal test (e.g. FTA) —> Reactive —> Syphilis
—> Reactive —> Treponemal test (e.g. FTA) —> Non-reactive —> negative for Syphilis (i.e. Other agents)
—> Non-Reactive —> negative for Syphilis

25
Reverse screening algorithm
Treponemal specific test (e.g. EIA) —> Reactive —> Non-treponemal test (e.g. RPR) —> Reactive —> Syphilis —> Reactive —> Non-treponemal test (e.g. RPR) —> Non-reactive —> confirm with ***2nd Treponemal specific test (e.g. TPPA) —> Reactive —> Syphilis (if Non-reactive: negative) —> Non-Reactive —> negative for Syphilis
26
Chancroid
***Rare in HK caused by Bacteria Empirical treatment: - ***Azithromycin single dose - ***Ceftriaxone single dose Work up 1. Gram-smear —> ***NOT reliable 2. ***Culture —> e.g. ***Hammond gonococcal medium —> can be problematic (many labs don’t have medium) 3. ***Diagnosis presumed if no evidence of Syphilis / HSV
27
Syndromic approach for Urethritis / Genital ulcer
Magic combination: Azithromycin (single dose) + Ceftriaxone (single dose) Cover: 1. GC 2. CT 3. Chancroid Check: - NOT Herpes ***clinically - Always consider Syphilis (no lesions, use ***blood samples) and HIV (must obtain consent) ∵ asymptomatic If above doesn’t work —> Consider alternative diagnosis / Refer
28
Why not just treat by clinical diagnosis / syndromic approach?
Single dose antibiotic high effective, few SE HOWEVER, workup is important: 1. Medico-legal case (rape, sex abuse) 2. Epidemiology (baselines, outbreaks, strain typing) 3. Antibiotic susceptibility tests (if resistance high, may need to abandon existing 1st line agents)
29
3. Genital lumps (Male / Female)
Causative agent: HPV (Human papilloma virus) - >100 types - all infect skin / mucosal surface - >=40 infect genital area - Warts: penis, vulva, perineal regions - incubation period 1-6 months - ***most infection self-limited, asymptomatic —> unrecognised - ***Treatment: symptomatic —> removal of warts - ***16, 18 esp. associated with Cervical cancer Clinical presentation: - Genital warts (椰菜花) Diagnosis: - ***Clinical diagnosis (unique enough) - CANNOT be cultured - NO routine serology tests available - HPV tests available to detect Oncogenic types in context of Cervical cancer screening —> but NOT suitable as general STD test
30
HPV types and diseases
NOT all sexually transmitted ***Molecular tests to distinguish between types Skin disease 1. Plantar warts (1, 4) 2. Common warts (2, 4, 7) 3. Flat warts (3, 10) Mucocutaneous disease 1. Genital warts ***(6, 11) 2. Laryngeal papillomata ***(6, 11) 3. Oral papillomata (2, ***6, ***11, ***16, ***18, 57)
31
***Summary
Urethral discharge: 1. Gonorrhoea Urethritis (淋病/白濁) 2. Non-gonococcal urethritis (NGU) —> Chlamydia trachomatis (衣原體) Genital ulcers: 1. Syphilis (梅毒) 2. Herpes simplex (生殖器疱疹) 3. Chancroid (軟性下疳) Genital lumps: 1. HPV (6, 11, 16, 18)