L30: Dysuria Flashcards
Urethritis in males
- 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)
Physiological discharge in males
Littre’s glands (urethral glands) produce colloid secretion containing glycosaminoglycans, protects epithelium against urine
Vaginal discharge
- Physiological: cyclical variation, some cervical mucus
- Cervicitis: endocervical infection (and inflammation involving transformation zone)
- Mucopurulent cervicitis e.g. gonorrhoea, chlamydia
- “Strawberry cervix” (Colpitis macularis - inflmmatory punctate haemmorhage) due to trichomonas - Genital candidiasis
- Bacterial vaginosis
- Other e.g. atrophic vaginitis (post-partum), foreign body
Chlamydia
- 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)
Chlamydia lifecycle
- 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)
Chlamydia - spectrum of disease
Males: urethritis, epididymitis, proctitis, Reiter’s syndrome
Female: cervicitis, pyuria, PID (+ectopic pregnancy), perihepatitis, infertility
Neonatal and paediatric: conjunctivitis (follicular), pneumonia, otitis media
Chlamydia pathophysiology
- 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)
Diagnosis of chlamydia
- 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
Which tests are better for diagnosis of chlamydia?
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
Treatment of uncomplicated chlamydial infection
- 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
Azithromycin action
- 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
Complications in of chlamydia in males
- 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%
Neisseria gonorrhoea
- Gram neg diplococcus
- Humans are only natural host
- Infect non-cornified epithelial cells
- Oxidase positive
- Fastidious growth
- Chromsomal or plasmid mediated antibiotic resistance
N. gonorrhoea defence mechanisms
- Pilin: adherence, resistance to neutrophils, antigenic variation
- Opa proteins: adherence, phase variation
- LOS: tissue toxin, antigenic variation
- Serum resistance
- IgA protease
N. gonorrhoea specimen collection and transport
- 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)
N. gonorrhoea growth and identification
- 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)
N. gonorrhoea - urethral infection in males
- 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
Diagnostic techniques for N. gonorrhoea
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
Treatment of uncomplicated gonorrhoea
- 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
Ciprofloxacin action
- 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
Gonorrhoea - complications in males
- Epididymitis (most common, unilateral testicular pain and swelling)
- Lymphangitis: generalised penile oedema
- Urethral stricture: rare
Rectal gonorrhoea infection
- 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)
Pharyngeal gonorrhoea infection
- 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)
Endocervical gonorrhoea infection
- 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
Gonorrhoea - complications in females
- 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
PID
= 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)
Treatment and complications of PID
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
Non-specific urethritis
- 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
Trichomonas vaginalis
- 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