Dysuria: Urethritis, Cervicitis and Testicular Pain

Question 1

How do you define Urethritis?

Answer 1

• Urethritis is an inflammation of the urethra, and is not the same as a urinary tract infection (UTI).
• In symptomatic males you will see increased PolyMorphicNuclearLymphocytes per HPF on microscopy of a urethral smear
• Symptoms are of an anterior urethritis;
  
  • Discharge, dysuria
• Criteria varies
• Can be misleading, eg you may see this post-ejaculation

Question 2

Where does the discharge come from in Urethritis in men?

Answer 2

• From Litres Glands that line the urethra
• A colloid secretion contains GAGs that protect the epithelium against urine.

Question 3

What are the potential causes of Discharge in women?

Answer 3

• Physiological: usually this!
  
  • M. Cyclical variation
  • Cervical Mucus: as the urethra is too short to contribute much
• Cervicitis
  
  • endocervical infection (and inflamm. invovling TZ)
    
    • mucoprulent cervicitis eg; gonorrhoea or chlamydia
    • Strawberry cervix* rare, infection
• Genital Candidiasis
• Bacterial Vaginosis (BVAB)
• Other Atrophic vaginitis, foreign body

Question 4

Chlamydia: who gets it, is it symptomatic and can they generate energy?

Answer 4

• Most common STI
• Usually in the Serially monogamous rather then promiscuous
• Rarely Fatal, commonly asymptomatic
• Obligate intracellular bacterium (‘energy parasite’) with complex biphasic lifecycle (24-48hrs): no ability to generate enrgey, instead take over host cell ATP production
  
  • can only take over once inside host cells

Question 5

What are the Reproductive cycle of the Chlamydia bacterium

Answer 5

• have a ‘bimorphic lifestyle’
• Elementary body that is an extremely infectious particle that can attatch to cells and be phagocytosed into
  
  • once inside, it can now use the cell to generate energy and turn into a much larger ‘Reticular Body”
• Reticular Body can then produce/release lots more elementary bodies
• This reproductive occurs over 24-48hrs; In order for antibiotics to be effective (need to cover 2 RC’s to work)
  
  • treatment is therefore 4-5 days

Question 6

Outer membrane of CHlamydia?

What are the serovars and what do they cause?

Answer 6

Similar to that of other gram negative bacteria

• Serovars: that cause distinct infections
  
  • A-C infect squamous (endemic trachoma)
  • D-K: genitourinary disease
  • L1,L2,L3 cause lymphogranuloma venereum (lymphatic damage)

Question 7

What’s the spectrum of disease that can be caused in both males and femals from D-K Serovar Chlamydia? (genitourinary diseases)

Answer 7

Males:

• Urethritis
• Epididimytis
• Proctitis
• Reiter’s syndrome

Female:

• Cervicitis
• Sterile pyuria
• PID (&ectopic pregnancy)
• Perihepatitis
• infertility

Neonatal and Paediatric

• Conjunctivitis
• pneumonia
• otitis media

Question 8

Pathophysiology of Chlamydia?

Answer 8

• Initial infection is mild and self Limiting!
• Antibodies against the major outer membrane (MOMP) can neutralise organisms
  
  • latent infection is induced, cause problems later
• Short term serovar-specific imunity developing
• Recurrent infection produces severe inflammation (resulting in tissue damage and scarring)
  
  • dueto exaggerated host CMI response
  • Cross-reacting heat shock protein aggravated by persisting intracellular chlamydia antigen (Chsp60) that looks like Human HSP!!

Question 9

How do you diagnose Chlamydia

Answer 9

• DNA amplificaation (nucleic acid amplification)
• Have increased sensitivity : detect
  
  • EIA ehich detects log 5-7 (not v sensitive)
  • culture which detects log 1-2
• Have increased specificity over EIA
• Obviates most of the problems with false positives
• PPV and NPV better then other tests
• Fewer storage and handling problems compared swabs for culture
• Can be automated

Question 10

How do you do specimen collection in males and females?

Answer 10

Males:

• FVU in both symptomatic and asymptomatic men

Females:

• vulvovaginal swab for NAAT
• Speculum examination is still recommended in symptomatic female patients

Question 11

Treatment of uncomplicated Chlamydial infection

Answer 11

1. Azithromycin (1gm stat)
   
   • equally efficacious to doxycycline
   • high level of patient adherence
   • pregnancy category B1
2. Doxycycline 100mg bid 7 days more pop.
   
   • efficacy 97-100%
3. ​Pregnany or breastfeeding women se
   
   • Azithromycin 1 g stat
   • Amoxycillin 500mg tid for 7 days
     
     • ​if you use you need to test 3-4 wks after to make sure
4. Uncomplicated infection needs the presence of effective Antimicrobial therapies for at least 2 reproduc. cycles.

Question 12

Azithromycin as a treatment?

Answer 12

• Azalide (macrolibe subclass)
• Inhibits translation of bacterial mRNA
  
  • binding to 50S subunit of the bacterial ribosome
• 3-5% patients: GI side-effects
• Tissue levels >50x plasma levels (long tissue t_1/2)
• Risk factor for long QT syndrome
• Chlamydia: resistance rare

Question 13

How do you approach the patients partner in terms of treatment?

Answer 13

• Partner Notification
  
  • all partners within the last 60-90 days
  • or last partner if >60 days ago
  • Test of cure NOT required ( may get false + )
• Treat partner(s) even if test negative
• Expedited partner treatment
  
  • PDPT a possibility in some jurisdictions
• Advise to practise protected sex during treatment

Question 14

Complications arising from Chlamydia in Males…

Answer 14

• Epididymitis (1-2%) and Infertility
• Reiters Syndrome
  
  • sexually acquired reactive arthritis
  • articular disease
  • often with ocular involvement (conjunctivitis, uveitis)
  • Females can get to as Erosive volvitis
• 20% have increased PMNL in prostatic secretion but prostatitis rare
• Conjunctivitis 1-2%

Question 15

Gonorrhoea rates in NZ

Answer 15

• not uncommon in auckland
• sits in late adolescant-young adult range
• But older in males

Question 16

Neisseria gonorrhoea

Answer 16

• Gram negative diplococcus
• Humans only natural host
• Infect non-cornified epithelial cells
  
  • intracellular replication
• Oxidase +
• Fastidious growth
• Chromosomal or plasmid mediated AB resistance
  
  • quick adaptive and good at dodging host defences

Question 17

Pathogenic and Defence mechanisms!

Answer 17

• Pilin
  
  • adherence
  • resistance to neutrophils
  • antigenic variation
• Opa proteins
  
  • adherence
  • phase variation
• LOS
  
  • tissue toxin
  • antigenic variation
• Serum resistance
  
  • sialylation of LOS
• IgA₁ protease

Question 18

Where/how do you collect and transport gonnorhea samples?

Answer 18

• ALways away from the site with symptoms/signs and also from other areas identified in sexual history at risk
• IF symptomatic take a sample for culture
• Specimen for culture can be left at room temp for up to 5 h without loss of viability
• Amies or stuarts only for transport where inoculation of growth medium will occur within 4-8h
  
  • not overnight

Question 19

You can grow gonnorrhea on __________ either with a _______ or ______ medium

Answer 19

You can grow gonnorrhea on selective artificial media either with a New York City or Thayer Martin medium

SAMs: contain blood, other growth promoters, antibiotics. Some fastidious strains may be sensitive to vancomycin

NY medium: done when you can expect a clean ‘culture’ eg from urethra

THayer Martin: when you can expect a lot of other bacteria, other things in there to suppress the other stuff

Question 20

Once N. gonnorrhea is cultured, you can confirm it via a _______ and then speciate it by….

Answer 20

Once N. gonnorrhea is cultured, you can confirm it via a oxidase test and then speciate it by …..

• carbohydrate degredation testing
• enzyme substrate tests
• combination
• Sensitivity testing

Question 21

Urethral infection in males…

Answer 21

• Most are symptomatic
  
  • incubation period 1-14 days (2-5 common)
• Anterior Urethritis
  
  • ​discharge (pussy, thick) and dysuria
  • erythema of meatus is variable (meatitis)
• Untreated men (95% asymptomatic after 6 months)

Question 22

Although gram staining is really only good from the urethra, culturing is good…?

NAAT??

Answer 22

really anywhere

NAAT: high sensitivity but specificity depends on brand and method

eg: 2 targets for GU and 3 targets for extra-genital

Question 23

Treatment of Gonorrhoea is?

Answer 23

Uncomplicated: very easy to treat if you use

• high dose Ceftiraxone
• and concomitant azithromycin

If sensitivities known and sensitive

• ciprofloxacin with azithromycin
• Directly observed treatment (DOT)
  • (but 50% isolates are resistaant to ciprofloxacin)

DO NOT USE Aziithromycin as sole first line therapy to minimise risk of resistance developing, instead do concurrent anti-chlamydial therapy as co-infection with chlamydia is common

Contact trace all individuals in last 30-90 days

Question 24

Describe Ciprofloxain as a gonorrhea treatment and what are it’s issues?

Answer 24

• 2^nd generation fluoroquinolone
• Broad spectrum of action; excellent tissue penetration
• Inhibits DNA gyrase
  
  • bacterial DNA Seperation is impede and cell division inhibited
• Resistant organisms have mutated topoisomerases; so the drug can’t bind :(

Question 25

Complications of Gonorrhea in males?

Answer 25

• Epididymitis
  
  • most frequent
  • presents with unilateral tetiular pain and swelling
• Lymphangitis
  
  • generalised penile oedma
• Urethral Stricture
  
  • now rare

Question 26

Describe Rectal gonorrhea Infections

Answer 26

• May be symptomatic or asymptomatic
  
  • if symptomatic, may vary from painless discharge to overt proctitis with tenesmus and pain
• If men not a reliable indicator of occurrence of unsafe anal sex, but due to direct inoculation
• In women anorectal con-infection is common; generally asymptomatic and usually due to contiguous spread from the genital area

Question 27

Describe Pharyngeal Gonnorrheal infection

Answer 27

• Acquired through oral sex
  
  • usually peno-oral
• Usually asymptomatic but can have a sore throat
• very uncommon as sole site of infection
• Important to treat with ceftriaxone and azithromycin
  
  • under-treatment in pharyngeal infection probably sigificantly contributes to the emergence of resistance (eg other antibiotics)

Question 28

Describe Endocervical gonnorrheal infection

Answer 28

• Primary site of infection
• urethral infection also common
• incubation period
  
  • less certain than in men
  • if local syptoms develop this is usually within 10 days
• infections usually asymptomatic
• if symptomatic, commonly have vaginal discharge, dysuria, intermenstrual bleeding or menorrhagia
• only ~40% gram stain

Question 29

COmplicaions of Gonnorrhea in women?

Answer 29

• PID occurs in an estimated 10-20% of women with acute infection
• GOnococcal PID is often more severe than non-gonococcal PID but rates of tubal involvement are similar
• Bartholins abscess, Skene’s abscess are less common complications

Question 30

Learn about PID

Answer 30

• Treatment has to be high dose for a long time (>2weeks)
• REpeated infection leads to increased inflammation → infertility
  
  1. 10-15%
  2. 25-35%
  3. 50-75%
• Lots of PID is Silent

Question 31

Disseminated Gonococci infection?

Answer 31

• Occurs in 0.5-3% cases
• Most commonly as dermatitis-arthritis syndrome
• Risks for DGI are female gender, post-menstruation, pharyngeal or asymptomatic infection, complement deficiency
• Proving infection microbiologically can be hard
• can occur in males

Question 32

Non-Specific Urethritis (when we don’t know what’s causing it)

Answer 32

• Diagnosis (really just a label) of NSU depends on
  
  • presence of symptoms or signs
  • microscopy of a urethral smear looking for PMNL (note that false + do occur)
  • rule out infection w chlamydia and gonorrhea
• Other pathogens can cause ‘NSU’
  
  • trichomonas vaginalis (more likely to be symptomatic as a cause of VDx in women but can be transiently symptomatic in men but is inhibited by the Zn present in prostatic secretions)
  • Mycopplasmuc genitalium : gives similar pictue as chlamydia with mild urethritis
  • candida
  • other ciruses or bacteria
    *