Reproductive System Week 6

Question 1

What is the difference between an STI and an STD?

Answer 1

STI includes both asymptomatic and symptomatic cases

STD includes symptomatic cases only

Question 2

Give an example of a type of infection where sexual activity is a possible mode of transmission

Answer 2

BBV

Intestinal pathogens e.g. salmonella, shigella, giardia, entamoeba

Question 3

Describe some common STDs, the causative organism and their approximate incidence in the UK in 2015

Answer 3

Genital warts and cancer - Papillomaviruses - 68,310(warts) (decreased by 7%) - vaccine
Urethritis, LGV - Chlamydia trachomatis - 200,288 (decreased by 4%) - screening and public health campaign
Genital herpes - Herpes simplex - 31,777
Gonorrhoea - Neisseria gonorrhoeae - 41,193 (increased by 11%)
Syphilis - Treponema pallidum - 5,288 (increased by 20%)
Non-specific GI - 42,262 (decreased by 10%)
Other (chancroid/LGV, HIV, Molluscum contagiosum, scabies, pediculosis pubis, trichomoniasis - 44,976
Total STI - 434,456 (decreased by 3%)

Question 4

Describe the at-risk groups for an STI/STD

Answer 4

Young
Certain ethnic groups
Low socioeconomic status groups
Aspects of sexual behaviour e.g. age at first sexual intercourse, number of partners, sexual orientation, unsafe sexual activity

Question 5

Describe some reasons why there has been an increased incidence of STIs between 1995 and 1999

Answer 5

Increased transmission - changing sexual and social behaviour, incresing density and mobility of populations
Acceptability of GUM services - increased attendance
Greater public, medical and national awareness (campaigns)
Development in diagnostic methods - screening programs

Question 6

Why will data from GUM services underestimate the true incidence of STIs ?

Answer 6

patients may be seen in a variety of other settings - GP, family planning clinics
Many infections are asymptomatic - e.g. thought that only 10% chlamydia cases may attend GUM services

Question 7

What factors affect the burden of STIs?

Answer 7

Acute and chronic/relapsing infections
Stigma - impact of diagnosis and tracing contacts
Consequent pathology - PID and infertility, reproductive tract cancers
Disseminated infections
Transmission to foetus/neonate

Question 8

How are STIs diagnosed?

Answer 8

Patient presents with genital lesions/problems to GP or GUM clinic - ulcers, vesicles, warts, urethral discharge or pain, vaginal discharge
Clinician notes non-genital clinical features suggestive of STI - disseminated disease
Detection of asymptomatic cases (contact tracing/screening)

Question 9

Describe the management of STIS

Answer 9

Treatment preferably single dose/short course
Co-infections common - screen and consider empiric treatment for other STIs
Consensus UK national guidelines
Contact tracing - patient and public health management
Sexual health education, advice on contraception and detailed instruction on the practice and need for safer sex

Question 10

Describe Human papillomaviruses, their diagnosis, treatment, screening and vaccines

Answer 10

> 100 types
DNA virus
Most common viral STI (4% young adults in lifetime)
Clinical consequences:
cutaneous, mucosal and anogenital warts (M=F) - benign, painless, verrucous epithelial or mucosal outgrowths (mainly HPV6 and 11) - vast majority of infected individuals fail to develop warts
cervical cancer (most common cancer in women 15-34) and anogenital cancer (high risk oncogenic - HPV16 and HPV18 - >70% cervical cancers)

diagnosis - clinical, biospy and genome analysis, hybrid capture

treatment - none - spontaeous resolution (70% 1 yr, 90% 2 yrs)
topical podophyllin, cryotherapy, intralesional interferon, imiquimod, surgery

screening - cervical pap smear cytology
colposcopy and acetowhite test
cervical swab - HPV hybrid capture (40% of 20-24 yr olds positive)

Vaccine - cervarix (HPV 16 and 18) - initally used in UK
gardasil (HPV 6,11,16 and 18) from 2011
offered to girls 12-13 (2 doses)
99% effective in preventing HPV 16 and 18 - related cervical abnormalities in those not already infected

Question 11

Describe Chlamydia trachomatis, its clinical consequences in females and males, diagnosis, treatment and screening

Answer 11

Obligate intracellular bacterium - dont grow on routine lab media
Infective form is elementary body which develops within host cell into reticulate body
reticulate body replicates eventually revertine back to elementary bodies which leave cell to infect other cells
Non-specific genital chlamydial infections - serotypes D-K
Makes up nearly half of all STIs diagnosed- 50% diagnosed in GUM, 50% from screening

Clinical consequences:
Males - urethritis, epididymitis, reiters syndrome(urethritis, conjunctivitis and arthritis), prostatitis, proctitis
Females - organism infects and replicates within epithelium of cervix and urethra - majority asymptomatic, important cause of mucopurulent cervicitis, urethritis (dysuria and frequency), ascending infection with UGT involvement can result in clinical or subclinical PID presenting as endometritis or salpingitis (PID leads to tubal damage, infertility and ectopic pregnancy), rarely perihepatitis
Both - oral inoculation - conjunctivitis
Neonatal infection - cervical infection in pregnancy - inclusion conjunctivitis - may progress to neonatal pneumonia if untreated
Many cases asymptomatic - especially in women

Diagnosis:
>200 000 cases diagnosed each year (nearly half of all STIs)
Endocervical(after pus removed from cervix)/urethral swab and urethral swabs - NAAT
1st void urine (urine less sensitive than endocervical swab) - NAAT
Neonatal infection - conjunctival swab (after pus removal, invert eyelid, scrape conjunctiva surface) - NAAT - Pneumonia serology WCC may show eosinophilia
Immunofluorescence - specimen fixed - stained with monoclonal antibody tagged with fluorescein - UV microscope - observer error, time consuming so only small no. of specimens - quality of specimen can be assessed
EIA - large number of specimens processed with ease - kits vary in sensitivity and specificity but some good - relatively cheap
PCR - high sensitivity and specificity - specimen may contain inhibitors that interfere, kits may yield significant false positives and negatives - EIA or PCR debate for population screening

Treatment:
tetracyclines (Doxycycline) or macrolides (azithromycin)
erythromycin in children
conjunctivitis - more widespread infection - systemic antibiotics

Screening:
sexually-active under 25s
urine (Mand F) or swab (F)
Nucleic acid amplification test (NAAT) - dual testing with N. gonorrhoeae available

Question 12

Describe Herpes simplex virus, its diagnosis, treatment and prevention

Answer 12

Primary genital herpes - extensive painful genital ulceration, dysuria, inguinal lymphadenopathy, fever
Usually associated with HSV 2 (HSV 1 causes cold sores)
Recurrent infection is asymptomatic to moderate (latent infection in dorsal root ganglia (as in chickenpox))
Diagnosis: PCR of vesicle fluid and/or ulcer base
Treatment: aciclovir (primary and severe disease)
Prevention: aciclovir prophylaxis for frequent recurrences
Barrier contraception - reduce risk of transmission

Question 13

Describe Neisseria gonorrhoeae, its diagnosis, treatment and prevention

Answer 13

Gram negative intracellular diplococcus
Likes to multiply inside white cells

Clinical consequences:
Males - urethritis (purulent discharge), epididymitis, prostatitis, proctitis (MSM) and pharyngitis (MSM)
Females - asymptomatic, endocervicitis, urethritis, PID (may lead to infertility)
Disseminated gonococcal infection - bacteraemia, skin and joint lesions (can cause septic arthritis and reactive arthritis)

Diagnosis:
Swab urethra, throat or rectum 
Urine NAAT
Gram stain
Fastidious - requires special media

Treatment:
Ceftriaxone (IM) (cephalosporin) - still some resistant strains
All patients tested and treated for chlamydia with azithromycin which may help prevent resistance to cephalosporin

Question 14

Describe syphilis, its diagnosis, treatment and prevention

Answer 14

Treponema pallidum (spirochaete)
Most cases men and MSM
Multistage disease, able to stick around for years
Primary stage - indurated, painless chancre (ulcer) - gradually heals
Secondary stage - 6 to 8 weeks later - fever, rash (anywhere), lymphadenopathy, mucosal lesions (mouth) - might not relate to the chancre
Latent stage - asymptomatic for years
Tertiary stage - neurosyphilis (GPI tabes dorsalis - general paralysis of the insane), cardiovascular syphilis, gummas
Congenital syphilis - screen pregnant women

Diagnosis: organism cannot be grown - dark field microscopy required
Screening with ELISA –> +ves RPR, TPPA, serologic pattern interpreted (possibility of disease, stage, response to treatment )

Treatment: penicillin + test of cure follow up

Question 15

What are some other causes of inguinal lymphadenopathy?

Answer 15

Lymphogranuloma venereum - C.trachoma serotypes L1,2,3
Rapidly healing papule than inguinal bubo (abscess)
Clusters in Europe (MSM)

Chancroid (Haemophilus decreyi) - painful genital ulcers

Granuloma inguinali /donovanosis (klebsiella granulomatis) - genital nodules –> ulcers

Question 16

What is trichomoniasis?

Answer 16

STI caused by a flagellated protozoan called trichomonas vaginalis
Causes thin, frothy, offensive discharge
Irritation, dysuria, vaginal inflammation

Diagnosis: vaginal wet preparation with or without culture enhancement

Treatment: metronidazole

Question 17

Describe vulvovaginal candidiasis, its diagnosis, treatment and risk factors

Answer 17

Candida albicans and other candida - may be part of normal GI and genital flora

Risk factors: antibiotics, oral contraceptives, pregnancy, steroids, diabetes, obesity

Profuse, white, itchy, curd-like discharge

Diagnosis - high vaginal smear (with or without culture)

Treatment - topical azoles (pessary or cream) or nystatin, or oral fluconazole

Not necessarily sexual

Question 18

What kinds of lice can spread sexually?

Answer 18

Scabies

Pediculosis pubis - distinct from body lice - crab louse (phthirus pubis)

Question 19

Describe bacterial vaginosis, its diagnosis and treatment

Answer 19

Perturbed normal flora - Gardnerella, mycoplasma, anaerobes
Scanty but offensive fishy discharge - not itchy - creamy

Diagnosis:
Vaginal pH >5, KOH whiff test
Lab - HVS gram stained smear
'Clue' cells - epithelial cells studded with coccobacilli
Reduced lactobacilli
Absence of pus cells

Treatment: metronidazole

Question 20

Describe the organism mycobacterium chlamydiae

Answer 20

Obligate intracellular bacteria
Dont grow on media

Infective form - elementary body - develops in the host cell into the reticulate body - replicates eventually reverting back to elementary bodies –> leave to infect other cells

Question 21

Describe the chlamydia infection in females

Answer 21

Commonly asymptomatic
Replicates within epithelium of cervix and urethra
Mucopurulent cervicitis, acute urethral syndrome (dysuria and frequency - common in young sexually active women)

Ascending infection can occur - can result in clinical or subclinical PID - endometritis or salpingitis - can lead to tubal damage, infertility and ectopic pregnancy
perihepatitis is a rare complication - gonorrhoea also causes this

Ocular infections common

Cervical infection in pregnant women - source of infection in the neonate - neonatal conjunctivitis common - untreated may progress to neonatal pneumonia

Diagnosis - endocervical swab - remove any pus before collecting - urine not as good for diagnosis (not as sensitive) but more useful for screening as easier for individuals, doesnt require staff member and is more acceptable

Question 22

Describe the chlamydia infection in males

Answer 22

Usually presents as urethritis

Complications - acute epididymitis
- Reiters syndrome - reactive arthritis resulting from infection - urethritis and conjunctivitis in the classical triad of symptoms - predominantly occurs in males

Diagnosis - urethral swab or first catch urine

Question 23

Describe the chlamydia infection in neonates

Answer 23

Commonly from infected mother
Conjunctivitis common
May progress to pneumonia if untreated

Eye swab – Remove any pus. Invert eyelid and scrape conjunctiva surface to obtain cellular material
Pneumonia – Serology is useful. A differential on a WCC (white cell count) may show eosinophilia.

Question 24

Describe the methods employed for chlamydia detection

Answer 24

Immunofluorescence
Specimens may be fixed to a slide and stained with a monoclonal antibody that is tagged with fluorescein.
Slides are examined under an ultraviolet microscope
drawbacks are that results are subject to observer error and the method is time consuming and therefore only suitable for small numbers of specimens
One advantage is that the quality of the specimen in terms of cells can be assessed using this technique.

Enzyme Immunoassays (EIA) 
Such tests allow large numbers of specimens to be processed with relative ease.  Commercial kits may vary in their sensitivity and specificity, but some kits have good sensitivity/specificity.  The tests are relatively cheap.
Molecular Methods (PCR, polymerase chain reaction)
Molecular methods offer high sensitivity and specificity, however clinical specimens may contain inhibitors that will interfere with the assay, and commercial kits may yield significant false positives and negatives.  
Studies are currently underway to ascertain whether EIA or molecular methods should be used for population screening.

Question 25

Describe the treatment of chlamydia infections

Answer 25

Chlamydia trachomatis contain relatively little peptidoglycan, the target for β lactam antibiotics.  The mainstay of treatment is the macrolides (erythromycin/clarithromycin/azithromycin) and tetracyclines (doxycycline).  
As conjunctivitis (both neonatal and adult) is part of a more widespread infection, this should always be treated with systemic antibiotics.

Question 26

Describe the gonorrhoea infection in females

Answer 26

The gonococcus primarily infects the cervix and urethra. This may lead to an acute cervicitis with vaginal discharge and “urethral syndrome” where the urethra is infected

Complications: Pelvic Inflammatory Disease: occasionally with tubo-ovarian abscess
Bartholins abscess
Disseminated gonococcal infection: a rare complication that affects women more than men. The common symptoms are pain on the joints, tenosynovitis and rash.
Perihepatitis

Diagnosis - Endocervical swab, urethral swab, rectal and pharyngeal swab

Question 27

Describe the gonorrhoea infection in males

Answer 27

Gonococal urethritis
Complications: Epididymitis
Disseminated gonoccocal infection

Diagnosis - urethral, rectal and pharyngeal swabs

Question 28

Describe the methods employed to diagnose gonorrhoea

Answer 28

Neisseria gonorrhoeae is a fragile organism and does not survive transportation well. Ideally specimens should be taken and plated directly on to media at the bedside (as occurs in GUM clinics).
Gram stain – the characteristic appearance of gram-negative diplococci allows a presumptive diagnosis to be made on the basis of the gram stain in some patients.
Culture/Sensitivities
Culture is far more sensitive than microscopy. Organisms that resemble Neisseria on culture must be confirmed as Neisseria gonorrhoeae on the basis of biochemical tests in order to distinguish them from other species. Sensitivity testing is important, as antibiotic resistance patterns are valuable in guiding future management guidelines.

Question 29

Describe the treatment of gonorrhoea

Answer 29

Neisseria gonorrhoeae may vary in its sensitivity. Initial therapy is usually guided by severity of symptoms and local knowledge of sensitivity patterns. Penicillin resistance is common

Question 30

Describe HPV

Answer 30

Genital warts caused by HPV are the commonest STI diagnosed at genitourinary medicine (GUM) clinics throughout the United Kingdom: First episode, recurrent and re-registered cases accounted for 22% (131 140 of 590 909) of all diagnoses in GUM clinics in 1999. More than 100 HPV types have been described, however, the vast majority of infected individuals fail to develop warts. Apart from being unsightly and difficult to treat, the main concern with this virus is the strong association of certain high risk types with cervical carcinoma.

Question 31

What is pelvic inflammatory disease ?

Answer 31

The result of infection ascending from the
endocervix, causing endometritis, salpingitis,
parametritis, oophoritis, tubo-ovarian abscess
and/or pelvic peritonitis

Question 32

Describe the pathophysiology behind PID

Answer 32

Ascending infection from the endocervix and
vagina
Infection causes inflammation
Inflammation causes damage
– Thus damaged tubal epithelium
– Thus adhesions form
Some tubal epithelium recovers but normally not total recovery –> infertility and ectopic pregnancy

Question 33

Describe some complications of PID

Answer 33

Ectopic pregnancy
Infertility
Chronic pelvic pain
Fitz-Hugh-Curtis Syndrome – RUQ pain and peri-hepatitis following Chlamydial PID (10-15%)
Reiters syndrome - cant see, cant pee, cant bend at the knee

Question 34

Describe the aetiology of PID

Answer 34

Often polymicrobial
Sexually transmitted infections:
– C. trachomatis
– N. gonorrhoea
Others:
– Gardnerella vaginalis, mycoplasma, anaerobes (BV)
- Actinomycetaceae - found in many body cavities (mouth/bowel/fallopian tubes) - IUD copper - long-term (8 years or more) - over time may damage womb lining allowing bacteria to penetrate the deep tissue (very rare)

Question 35

Describe the epidemiology of PID

Answer 35

Underestimated (asymptomatic)
Sexually active women – Peak 20-30 years old
Incidence rate in primary care approximately 280 per 100,000py

Question 36

What are the risk factors for PID?

Answer 36

As for STIs
– Young age
– Lack of use of barrier contraception
– Multiple sexual partners
– Low socioeconomic class 

IUCD - putting it in and removing it

Question 37

What are the clinical features of PID?

Answer 37

History 
• Pyrexia 
• Pain
– Lower abdominal pain
– Deep dyspareunia (pain having sex)
• Abnormal vaginal/cervical discharge 
• Abnormal vaginal bleeding - friable, post coital, intermenstrual
• Sexual history & prior STI 
• Contraceptive history
Examination 
• Fever (usually>38)
• Lower abdominal tenderness which is usually bilateral 
• Bimanual examination (abscess)
– adnexal tenderness (tubes, ovaries)
– Cervical motion tenderness
• Speculum examination
– Purulent cervical discharge 
– Cervicitis (red and inflamed)

Question 38

What is the differential diagnosis of PID?

Answer 38

Gynaecological:
Ectopic pregnancy
Endometriosis - menstrual cycle pain
Ovarian cyst complications - torsion - short term

Gastro- intestinal:
IBS
Appendicitis
Vomiting and nausea (only 50% of PID patients) - do they have an appendix?

Urinary
UTI - dipstick, frequency, dysuria

Other
Functional pain - Ongoing chronic pain in lower pelvis

Question 39

Describe the investigations for PID

Answer 39

Urinary and/or serum pregnancy test 
Endocervical and High vaginal swabs
– Presence of NG/CT supports diagnosis
– Absence of NG/CT does not exclude diagnosis - Large number not caused by
Blood tests
– WBC and CRP 
Screening for other STIs including HIV
Diagnostic laproscopy gold standard - benefit of adhesion lysis and drain abscesses if there - negatives - cost, risk of damaging, might not see any inflammation from outside of tubes etc

Question 40

Describe the management of PID

Answer 40

Low threshold for empirical treatment - analgesia, rest, management of sepsis
– Delayed treatment increases longterm sequelae
Severe disease requires IV antibiotics and admission for observation and possible surgical intervention
– Pyrexia >38, signs of tubo-ovarian abscess, signs
of pelvic peritonitis
– Increased risk of longterm sequelae

Contact tracing essential, full screen for woman

Outpatient treatment
IM Ceftriaxone 500mg STAT + PO Doxycycline 100mg BD + PO Metronidazole 400mg BD
Inpatient treatment
IV Ceftriaxone 500mg STAT + IV/PO Doxycycline 100mg BD + IV Metronidazole 400mg BD —–>
PO Doxycycline 100mg BD + PO Metronidazole 400mg BD

Treats all potential causative agents

Laparoscopy/laparotomy may be considered if
– No response to therapy
– Clinically severe disease
– Presence of a tubo-ovarian abscess
Ultrasound guided aspiration of pelvic collections is less invasive

Question 41

What should you tell a patient with PID?

Answer 41

What the diagnosis is
What treatment they are having
– Possible side effects
– Importance of completing antibiotics
What complications they are at risk of
– Risk of these increases with repeat episodes
How to reduce the risk of further episodes
Contact tracing
– Empirical treatment of partners
– Avoid unprotected sex until antibiotic course complete in self and partner