ERS36 Sexually Transmitted Disease Flashcards
STI
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)
Encounter + Entry of STI agents
- 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
Consequence / Complications of STI
- ***Pelvic inflammatory disease
—> infertility, ectopic pregnancy - Anogenital cancer (predisposed by HPV infection)
- Secondary / Tertiary syphilis
- Recurrent herpes infection
- Increase risk of HIV infection
- Adverse outcome of pregnancy
- Congenital diseases (e.g. Syphilis, Herpes) —> can be life-threatening to baby
Major STI in HK
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
***Clinical presentations of STD
Big 3:
1. Urethral discharge (Urethritis: Male)
2. Genital ulcer (Male / Female)
3. Genital lumps (Male / Female)
- Urethral discharge
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)
***Typical urethritis
- 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 - Non-gonococcal urethritis (NGU) —> Chlamydia trachomatis
- 7-14 days incubation
- **Gradual onset
- **Mild dysuria
- ***Little discharge
- Common relapse
Management of urethritis
- Establish presence of urethritis
- P/E + Microscopy (WBC, Bacteria) - 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 - Evaluate + Treat partner appropriately
- Follow-up examination (optional)
Drug treatment for urethritis
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
Chlamydial infections
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)
- Chlamydia pneumoniae —> Respiratory tract infection
- Chlamydia psittaci —> Psittacosis (respiratory tract)
Collection of sample from Penis, Anal canal, Cervix
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
***2 swabs
1st one for GC culture, 2nd one for CT culture
- 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
- 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
Pharyngeal gonorrhoea
AIDS / Immunocompromised: Gonococcal pharyngitis
Immunocompetent: Asymptomatic —> diagnostic difficulty
Alternative work-up approach
***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
- Genital ulcer (Male / Female)
- Single / Multiple
- With / without vesicles
- Different forms
- ***Syphilis (梅毒)
- ***Herpes simplex (生殖器疱疹)
- Chancroid (軟性下疳)
(4. Lymphogranuloma venereum LGV (rare)
5. Donovanosis (rare): by Calymmatobacterium granulomatis)
Syphilis vs Herpes vs Chancroid vs LGV vs Donovanosis
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)
Approach for genital ulcerations
If Typical syndrome
—> Lab tests may not be necessary
If Lab service limited
—> syndromic management approach may be used
***Genital herpes
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))
- ***Viral culture
- days
- positive up to 80% (depend on stage)
- Cytopathic effect in cell line (A549 cell) - Antibody test
- no use in diagnosis
Herpes infection
- 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
***Syphilis
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
Natural history of Syphilis
***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%)
***Microbiological diagnosis of Syphilis
-
**Serology
- Specific Ab detection
- **Mainstay approach - 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!!!
***Serological diagnosis of Syphilis
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)
Traditional screening algorithm
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
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
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
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
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)
- 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
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)
***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)
