L30: Dysuria

Question 1

Urethritis in males

Answer 1

• Condition occurring in symptomatic males with >5 PMNL (polymorphic nucleotides) per HPF (high power field) on microscopy of urethral smear
• May see some PMNLs on normal slide (e.g. if male ejaculated and not urinated 2-3hrs before sample)
• Symptoms of anterior urethritis (e.g. dysuria, discharge)

Question 2

Physiological discharge in males

Answer 2

Littre’s glands (urethral glands) produce colloid secretion containing glycosaminoglycans, protects epithelium against urine

Question 3

Vaginal discharge

Answer 3

1. Physiological: cyclical variation, some cervical mucus
2. Cervicitis: endocervical infection (and inflammation involving transformation zone)
   - Mucopurulent cervicitis e.g. gonorrhoea, chlamydia
   - “Strawberry cervix” (Colpitis macularis - inflmmatory punctate haemmorhage) due to trichomonas
3. Genital candidiasis
4. Bacterial vaginosis
5. Other e.g. atrophic vaginitis (post-partum), foreign body

Question 4

Chlamydia

Answer 4

• Most common bacterial STI in NZ (mainly young adults)
• Commonly asymptomatic, rarely fatal
• Outer membrane similar to other gram-neg bacteria (does not show on typical gram stain)

Question 5

Chlamydia lifecycle

Answer 5

• Obligate intracellular bacterium (energy parasite) with biphasic lifecycle (24-48hrs - need antibiotics for 2 cycles)
• Deficient in endogenous ATP production (use host cell ATP)
• Cannot grow on artificial media
• Elementary body (small,compact) phagocytosed by cells, takes over ATP production machinery and turns into larger reticulate body
• Reticulate body multiples producing elementary bodies (cell ruptures and release of elementary bodies)
• Serovars D-K cause GU disease (infect squamocolumnar cells)

Question 6

Chlamydia - spectrum of disease

Answer 6

Males: urethritis, epididymitis, proctitis, Reiter’s syndrome
Female: cervicitis, pyuria, PID (+ectopic pregnancy), perihepatitis, infertility
Neonatal and paediatric: conjunctivitis (follicular), pneumonia, otitis media

Question 7

Chlamydia pathophysiology

Answer 7

• Initial infection mild and self-limited
• Short term serogroup-specific immunity (few months)
• Recurrent infection causes severe inflammation (tissue damage and scarring): due to exaggerated cell-mediated immune response by cross-reacting heat shock protein (chlamydia heat shock protein similar to human heat shock protein)

Question 8

Diagnosis of chlamydia

Answer 8

• Sample collected: first void urine in men, vulvo-vaginal swab in women (+ speculum exam in symptomatic women)
• Enzyme immune assay (ELISA): not very sensitive, need high amount of organisms in sample
• DNA amplification (NAAT - nucleic acid amplification test): detects very low amounts of material, but be careful of established infection or just contamination, fewer storage/handling problems than swabs for culture

Question 9

Which tests are better for diagnosis of chlamydia?

Answer 9

NAAT > culture > EIA

• Modern NAATs similar in sensitivity and specificity
• SDA used currently but also PCR
• Can be performed on self-collected sample which remain stable at room temp for many days
• Some advancement in rapid point of care testing

Question 10

Treatment of uncomplicated chlamydial infection

Answer 10

• Preferred treatment is doxycycline for 7 days: efficacy 97-100%
• Azithromycin 1gm stat: similar efficacy in doxy in genital sites, can be given in clinic, concern about rising resistance
• In preg/breastfeeding: azithromycin 1gm stat or amoxicillin for 7 days (test of cure 3-4wks after finishing treatment)
• Uncomplicated infection needs effective antimicrobial treatment for at least 2 reproductive cycles (5 days)
• Complicated disease requires longer course
• Treat partners in last 60-90 days even if negative test + protected sex in treatment

Question 11

Azithromycin action

Answer 11

• Azalide (macrolide subclass)
• Inhibits translation of bacterial mRNA (binds to 50s subunit of ribosome)
• Long tissue half life: tissue levels > 50x plasma levels
• 3-5% have GI side effects (do not take on empty stomach)
• Risk factor for long QT syndrome
• Chlamydia resistance rare

Question 12

Complications in of chlamydia in males

Answer 12

• Epididymitis (1-2%) and infertility
• Reiter’s syndrome: reactive arthritis + ocular involvement (conjunctivitis, uveitis) or mucocutaneous involvement (note: Reiters can occur in females = erosive vulvitis)
• 20% have increased PMNL in prostatic secretion but prostatitis is rare
• Conjunctivitis 1-2%

Question 13

Neisseria gonorrhoea

Answer 13

• Gram neg diplococcus
• Humans are only natural host
• Infect non-cornified epithelial cells
• Oxidase positive
• Fastidious growth
• Chromsomal or plasmid mediated antibiotic resistance

Question 14

N. gonorrhoea defence mechanisms

Answer 14

1. Pilin: adherence, resistance to neutrophils, antigenic variation
2. Opa proteins: adherence, phase variation
3. LOS: tissue toxin, antigenic variation
4. Serum resistance
5. IgA protease

Question 15

N. gonorrhoea specimen collection and transport

Answer 15

• From site with signs/symptoms + other at risk areas from sexual history
• If symptomatic take sample for culture
• Specimen can be left at room temp for 5hrs (but do not tolerate drying out)
• Amies’ or Stuart’s for transport where inoculation of growth medium will occur within 4-8hrs (not overnight)

Question 16

N. gonorrhoea growth and identification

Answer 16

• 35-37 degrees, 5% CO2, pH 6.5-7.5, needs iron
• New York City medium (GU sites)
• Thayer Martin medium (more antibiotics, sites with other bacteria e.g. rectum, throat)
• Neisseria confirmed by positive oxidase test
• Species identified by carbohydrate degradation testing or enzyme substrate testing
• Sensitivity test: E test strip (MIC can be read directly)

Question 17

N. gonorrhoea - urethral infection in males

Answer 17

• Mostly symptomatic: incubation period 1-14 days (2-5 common)
• Anterior urethritis: discharge and dysuria, erythema of urethra variable (meatitis)
• Untreated men - 95% asymptomatic after 6months

Question 18

Diagnostic techniques for N. gonorrhoea

Answer 18

Gram stain:

• High accuracy from male urethra
• Cervix and rectum less sensitive/specific

Culture from site: relatively accurate from any site (with adjusting culture medium)

NAAT (nucleic acid amplification test):

• High sensitivity and specificity depends on brand, method and site (2 targets positive from GU samples, 3 from non-genital samples)
• High patient acceptability (can be self-collected)
• Still need culture for antibiotic resistance
• Chlamydia NAAT typically combined with gonorrhoea
• Molecular typing to confirm gonococcal strain

Question 19

Treatment of uncomplicated gonorrhoea

Answer 19

• If sensitivities unknown or breastfeeding/pregnant = ceftriaxone IMI stat, concomitant treatment with azithromycin 1g stat
• If sensitivities known and sensitive = ciprofloxacin 500g stat + azithromycin 1g stat (but 50% of isolates resistant to cipro)
• Do not use azithromycin as sole first-line (minimise risk of resistance increase)
• Concurrent anti-chlamydial therapy as co-infection common (ceftriaxone and azithro + doxy if known chlamydia)
• Contact trace 30-90 days

Question 20

Ciprofloxacin action

Answer 20

• 2nd generation fluoroquinolone
• Broad spectrum, excellent tissue penetration
• Inhibits DNA gyrase: inhibited cell division
• Resistant organisms have mutated topoisomerases so drug cannot bind
• Contraindicated in pregnancy, breastfeeding

Question 21

Gonorrhoea - complications in males

Answer 21

• Epididymitis (most common, unilateral testicular pain and swelling)
• Lymphangitis: generalised penile oedema
• Urethral stricture: rare

Question 22

Rectal gonorrhoea infection

Answer 22

• Symptomatic or asymptomatic
• Pain/painless discharge, or proctitis, tenesmus (sense of needing to defecate)
• In men not reliable indicator of unsafe anal sex (can be contaminated finger, transfer from genitalia)
• In women anorectal co-infection common (usually asymptomatic, spread from genitalia)

Question 23

Pharyngeal gonorrhoea infection

Answer 23

• Oral sex
• Usually asymptomatic, sometimes mild sore throat
• V. uncommon as only site of infection
• Important to treat with ceftriaxone and azithromycin (site of increasing resistance)

Question 24

Endocervical gonorrhoea infection

Answer 24

• Primary site of infection
• Urethral infection also common
• Usually asymptomatic
• Can have vaginal discharge, dysuria, inter-menstrual bleeding, menorrhagia
• Gram stain not effective so require lab based isolation

Question 25

Gonorrhoea - complications in females

Answer 25

- PID in 10-20% of women with acute infection - Gonococcal PID more severe than non-gonococcal - Bartholin's abscess, Skene's abscess are less common complications

Question 26

PID

Answer 26

= Pelvic inflammatory disease (complication of gonorrhoea) - If mild high chance of asymptomatic urethritis in male partner - If moderate/severe often due to mixed infection e.g. with chlamydia - Fitz-Hugh-Curtis syndrome = peri-hepatic pain and formation of adhesions (usually chlamydia) Microbial causes: polymicrobial, primary (chlamydia, gonorrhoea), secondary (BV organisms, others e.g. anaerobes)

Question 27

Treatment and complications of PID

Answer 27

Treatment: ceftriaxone + doxycycline with/without metronidazole Complications: - Chronic pain, subsequent PIC, infertility, ectopic pregnancy - Silent PID: 50-60% of women with infertility have serological evidence of previous chlamydia or gonorrhoea

Question 28

Non-specific urethritis

Answer 28

- Diagnosis largely depends on symptoms/signs + urethral smear for PMNL - Typically chlamydia and gonorrhoea - Trichomonas vaginalis - Mycoplasma genitalium = mild urethritis or asymptomatic, responds to azithromycin or moxifloxacin, only tested for in NZ with persistent NSU - Also herpes simplex virus, adenoviruses, N. meningitidis

Question 29

Trichomonas vaginalis

Answer 29

- Common cause of STIs esp. females - Protozoa with flagella (large, seen under light microscopy with no stain) - Infection may facilitate HIV transmission Males: - Transient in male tract, inhibited by high zinc in prostate secretions, infection usually symptomatic