Pathogens V: Sexual health and STIs

Question 1

What service caters for sexual health problems?

Answer 1

• Combined sexual health clinics

Question 2

What 5 things should a sexual health service provide?

Answer 2

1- Accessibility: local combined sexual health clinics
2- Confidentiality: just need contact number
3- Efficiency: >98% are seen within 2 working days
4- Open-mindedness
5- Positivity

Question 3

What are the big 5 sexually transmitted infections? What is their causative organism?

Answer 3

*All can be present without clinical symptoms

Question 4

What are the main viruses that cause STI?

Answer 4

• Human herpes (Human herpes virus)
• Anogenital warts (Human papillomavirus)

Question 5

What are the main bacterial causes of STI?

Answer 5

1. Chlamydia (Chlamydia trachomatis)
2. Gonorrhoea (Neisseria gonorrhoea)
3. Syphilis (Treponema pallidum)
4. Genital mycoplasmas (Mycoplasma genitalium)

Question 6

What is the “other” cause of STI?

Answer 6

Trichomoniasis (Trichomonas vaginalis)

Question 7

What are the 2 pathologies that aren’t sexually transmitted infections by strict definition?

Answer 7

1. UTIs - sexual contact can increase likelihood of exposure but doesn’t have to
2. Candidiasis (“thrush”) - overgrowth of Candida albicans due to changes in vaginal flora - not transmitted
3. Bacterial vaginosis - overgrowth of vaginal flora - not transmitted per se

Question 8

1- Why has gonorrhoea advanced to 2nd place from 4th place in big 5?

2- Why are we seeing a decrease in HPV infections?

3- Why Is syphylis so detrimental? What is offered to all patients as a result of this?

4- What age group does Chlamydia affect most

Answer 8

1- Resistance to antibiotics

2- Standard vaccination programme against HPV. Vaccination with GardasilTM covers two high-risk strains (16 & 18) for cervical (and other) cancer, but also the two most prevalent low-risk strains for anogenital warts (6 & 11).

3- Often missed as primary symptoms disappear in their own. Late syphilis infections are associated with severe CNS complications and death.
> Syphilis serology should be offered to all patients

4- 15-25 years of age

Question 9

What STI commonly recur?

Answer 9

• Anogenital warts (HPV) and Genital herpes (HSV) show almost 50% recurrence

Question 10

A significant, proportion of undiagnosed or treatment- refractory chlamydial infections go on to produce what disorder?

Answer 10

• Pelvic-inflammatory disorder
  > Extremely serious and a potential complication of many of STI if left untreated

Question 11

Why are HIV cases decreasing?

Answer 11

• Ability of us to identify cases and provide antiretroviral treatments.
  > If you can reduce a patient’s viral load to “undetectable” then the infection cannot be transmitted by that person.

A patient with an UNDETECTABLE viral load cannot transmit HIV at all!
-All your patients who come for an STI screen should be offered testing for HIV

Question 12

What are the 2 types of patients when it comes to STI?

Answer 12

• Symptomatic : symptoms guid you
  > May need treatments there and then
• Asymptomatic : patients may not have symptoms
  > Asymptomatic patients will need a little more questioning to discern what they might be at risk of.

Question 13

What questions would you ask patients to learn about their last sexual contact?
How do you ask about their past sexual history?

Answer 13

• You want to know if that site needs testing

*Past sexual history:
3 months is usually long enough. Ask all the same questions for each patient as for LSC

Question 14

What other areas would you need to investigate in sexual health history?

Answer 14

1- Patient’s medical history:
Include asking about previous STI diagnoses! Remember recurrence is a problem

2- Drug and alcohol use:
Includes chemsex. Also, smoking…

3- Blood-borne virus (BBV) risk:
Not just HIV – includes hepatitis as well.. if they have a hepatitis risk - how would you manage this whilst you wait for results

4- Assess pregnancy
It might affect what drugs a patient can take if you do decide to treat them.

Question 15

Women may need other questions asked such as…?

Answer 15

1- Last menstrual period:
2- Preferred contraception:
3- Pregnant women:
> Many (including the main ones) of the STIs can be passed from mother-to-child
> This can lead to trachoma, ophthalmia neonatorum and neonatal meningitis
4- Breastfeeding:
Affect certain drugs due to risk of excretion in breast milk

*This is also an opportunity to look out for anything else:
Abuse, FGM, etc.

Question 16

What follows questioning?

Answer 16

• Examination and sampling will follow, depending on the information you get!

Question 17

Anogenital herpes is caused by what?

Answer 17

• Human herpesviruses (HSV1 and HSV2) ; same as coldsores
  > Involves infection with virus or reactivation of pre-existing infection

Question 18

What HSV group do HSV1/2 belong to?

Answer 18

• Alphaherpesvirinae (dsDNA and enveloped)

Question 19

How does Anogenital herpes spread?

Answer 19

• Spread from person-to-person through secretions – HSV can infect any stratified squamous epithelium

> Extremely painful

Question 20

1- What HSV is the most common cause of herpes in the UK?

2- What HSV is more likely to cause recurrence?

3- How often do recurrent herpes episodes occur?

4- What fraction of patients develop symptoms?

Answer 20

1- HSV-1

2- HSV-2

3- 4 episodes

4- 1/3

Question 21

Name the 3 outcomes of infection from human herpesviruses (HSV1 and HSV2).

Answer 21

1. Symptomatic infection (~33%) resulting in the classic vesicular, painful rash
2. Latency in dorsal root ganglia… can lead to reactivation… which in itself can lead to…
3. Viral encephalitis – talked about in Pathogens IV

Question 22

Human herpesvirus has primary,secondary and recurrent infection. Explain this.

Answer 22

• Primary – No pre-existing Ig to virus
• Secondary – Pre-existing Ig to virus present
• Recurrent – Reactivation of latent infection

Question 23

How do doctor manage Anogenital herpes? What is the dilemma we have with managing herpes?

Answer 23

• Acyclovir
• Analgesia and reducing spread are key
  > Does not stop recurrence
  > The patient has prior T-helper cells and antibodies against the virus, but that does not stop them experiencing discomfort, embarrassment and risk of serious complications… nor does it stop them spreading it.

Question 24

What are the symptoms of primary Anogenital herpes infection?

Answer 24

• Painful, irritated papules arise on penis/vagina/vulva/anus or other mucosal tissues
  > Usually ulcerative, vesicular and exudative

Question 25

Describe the immune response to Anogenital herpes.

Answer 25

- Ongoing cell death and TH1 response lead to vesicles and ulcers with possible systemic symptoms of fever and myalgia - Symptoms abate at ~10 days - Generation of anti-virus CD8+ cytotoxic T-cells and neutralising Ig is responsible and results in memory *Symptoms are often less severe in patients with secondary infection! Papules and vesicles may be subclinical and identified only by specialist (or even non-visible)

Question 26

How do we detect Anogenital herpes?

Answer 26

- Samples from vesicular exudate at affected sites sent for nucleic-acid amplification tests (NAAT) to confirm virus - Virus serotyping by immune methods needed

Question 27

What causes Anogenital warts? - Name the Family - Name the Genus - Name the genome - Name the 2 groups the virus are split into/ what different symptoms do they cause?

Answer 27

- **Human papillomavirus (HPV)**= more than 120 types of papillomavirus > Family: Papillomaviridae > Genus: Papillomavirus > Genome: dsDNA = (non-enveloped)

Question 28

what are some cancers that can be caused by high risk HPV strains?

Answer 28

99% cervical cancers, 80-90% anal cancers, 36% oropharyngeal cancers, 50% penile cancers

Question 29

What do high risk/ low risk HPV do upon infection?

Answer 29

1. **Initial exposure to *stratum basale* cells** 2. **Lysogenic replication** - both alter the way the infected cell *enters and leaves the cell cycle:* > LOW RISK STRAINS: cause symptoms or no symptoms which may undergo ***lytic replication and spread*** → **cell-mediated and humoral clearance** > HIGH RISK STRAINS: cause **irreversible replication** with failures of error-checking → **tumour formation**

Question 30

What are the symptoms of primary anogenital warts infection? Warts can be asymptomatic what are the clinical implications to be aware of tho?

Answer 30

- Presence of warts on any squamous epithelium. > Classical features based on induced hyper-proliferation of stratum basale cells - Can be asymptomatic but still associated with transmission

Question 31

what are the 2 phases the immune system has for clearing the HPV infections (Anogenital warts) ?

Answer 31

- Th1 response will cause regression when cytotoxic T-cells begin to kill off the infected stratum basale cells that are infected - Seroconversion when antiviral IgG is produced to prevent any reinfection of cells.

Question 32

1- How are HPV infections detected? 2- How do we manage HPV infections? 3- What are the Complications of HPV infections?

Answer 32

1- Most are "classical" and diagnosed by presentation 2- Multiple management attempts needed especially in recurrent infections - drugs (podophyllotoxin, imiquimod) - physical ablation (cryotherapy or excision) can be used but problematic/unpleasant 3- - Recurrence is very common - Infection with high-risk strains does not produce symptoms, but can be a massive risk for precancerous change

Question 33

What are the 4 minimum infections to be tested for on a standard STI screen.

Answer 33

-Chlamydia -Gonorrhoea With serology for: -Syphilis -HIV

Question 34

What bacteria causes Chlamydia? What are the characteristics of this bacteria?

Answer 34

**Chlamydia trachomatis** - No true cell wall in Chlamydiae – dual membrane and capsular serotypes

Question 35

What are the 2 forms of the Chlamydia bacterium?

Answer 35

Question 36

Describe the infective cycle of Chlamydia bacterium?

Answer 36

Question 37

1- What serotypes of Chlamydia trachomatis cause LGV (lymphogranuloma venereum) 2- What stereotype lead to urogenital infection/transient conjunctivitis? 3- What stereotype cause ophthalmic infection? 4- What serogroup cause trachoma?

Answer 37

1- L1/L2/L3 2- D-K 3- All 4- A-C

Question 38

What are the primary symptoms of Chlamydia trachomatis? > What gender present as asymptomatic mostly?

Answer 38

**Non-gonococcal urethritis (NGU)** *Variety of symptoms depending on location - Urethritis is most common presentation, but anal, pharyngeal and conjunctival infections possible - Dysuria, discharge and pain are common. Women may have cervicitis, dyspareunia, IM/PC bleeding as well - Eye infections = Trachoma (leading cause of reversible blindness worldwide) > Men

Question 39

How is Chlamydia detected?

Answer 39

- Swab of symptomatic area or first-catch urine - NAATs for detection - Culture needed for antimicrobial sensitivity

Question 40

What are the complications of Chlamydia?

Answer 40

- Asymptomatic infections may persist for a year - Spread from primary site is a leading cause of pelvic inflammatory disease, epididymitis, orchitis and edometritis - Lead to infertility - Can lead to SARA (sexually-acquired reactive arthritis)

Question 41

Is chlamydia transmissible to new-born?

Answer 41

- Yes (often leading to ophthalmia neonatorum).

Question 42

1- What bacteria causes Gonorrhoea? 2- What are the characteristics of this bacteria?

Answer 42

1- **Neisseria gonorrhoea** = Gonococcal urethritis 2- - classic appearance as pairs of bean-shaped cocci - belongs to same genus as N. meningitidis - does NOT produce a capsule - thus no possibility of antibodies against it

Question 43

1- Where does primary infection of Gonorrhoea occur? 2- What are the primary symptoms of Gonorrhoea?

Answer 43

1- **Columnar mucosal epithelium** (urethra, rectum, pharynx and conjunctiva) 2- *As with chlamydia, location of infection is important as symptoms may be different* - Male patients (~90%) will show symptoms of gonococcal urethritis - Female patients (~50%) will show symptoms of cervicitis (urethritis rarer than men) > Other sites often asymptomatic but discharge and pain are most common symptoms

Question 44

What gender does Gonorrhoea mostly present?

Answer 44

- Males and mimic those of NGU. > Infections in other sites are likely following exposure and should be tested for based on the history results.

Question 45

How is Gonorrhoea detected in Asymptomatic and Symptomatic patients?

Answer 45

- Asymptomatic urethral infection should be investigated by: > first-catch urine (in males) > self- taken vulvo-vaginal swabs (in females) *and these should be subjected to nucleic-acid amplification tests (NAATs) for chlamydia and gonorrhoea.* > Microscopy is of limited use if there is no discharge (as the pathogen number will be sparse) but culture for ID and antibiotic sensitivities will be of use. - Symptomatic > Discharge from any site should be sampled by swab and should be investigated through microscopy as this may show N. gonorrhoea and allows for diagnosis in less than 1hr. > Culture of swabs is essential for antibiotic sensitivities

Question 46

What are the complications of Gonorrhoea?

Answer 46

- Uncontrolled infection will lead to deeper spread (PID and other damage to reproductive system) - Disseminated gonococcal infection through the blood can lead to serious problems in skin, joints, tendons - Long-term colonisation of deeper tissues can also be an issue, with infection flaring up again in places such as tendon sheaths. - Persistence at subclinical levels in genital and extragenital sites can be long-lasting (cannot become immune to gonorrhoea) - Babies may contract ophthalmia neonatorum during birth

Question 47

1- What is NGU now known to be caused by? What are the implications of this discovery?

Answer 47

1- NGU is now known to be caused by Mycoplasma genitalium, which shows a ~40% insensitivity to macrolides > Likely responsible for many treatment failures > Macrolide resistance in Chlamydia is increasing > Treatment regimens updated! If M. genitalium detected: 100mg oral **doxycycline** twice-daily for 7 days, followed by **azithromycin** 1g orally (stat), followed by 500mg per day for two days **Moxifloxacin**, oral 400mg once-daily for 10 days (where sensitivities known)

Question 48

What are the treatments for Chlamydia? ( Uncomplicated NGU) Name the alternatives we can give too.

Answer 48

- **100mg oral doxycycline twice-daily for 7 days** Alternatives: > **Azithromycin** 1g orally followed by 500mg per day for two days (should be considered sub-optimal) > **Ofloxacin** (oral 400mg once-daily for 7 days)

Question 49

What are the treatments for Gonorrhoea? (Uncomplicated gonococcal urethritis) What alternatives can be given?

Answer 49

**1g intramuscular ceftriaxone stat** - Alternatives: > **Gentamicin** (240mg intramuscular injection stat)PLUS 2g oral azithromycin stat > **Cefixime** (400mg oral stat) – if patient refuses injectionPLUS 2g oral azithromycin stat > **Ciprofloxacin** (500mg oral stat) – if cephalosporins contraindicated AND sensitivities known

Question 50

What complicates Gonorrhoea and Chlamydia treatments?

Answer 50

- Pregnancy and breastfeeding

Question 51

What MUST happen after treatment?

Answer 51

- Test of cure recommended for all patients! - Treatment failures MUST be reported

Question 52

What is the problem we have Neisseria gonorrhoea?

Answer 52

- One of the most dangerous antimicrobial resistance threats we have ever encountered. Since 1947 it has become resistant to benzylpenicillin, azithromycin, ciprofloxacin and now shows decreased sensitivity to ceftriaxone.