L39 Genital ulcers: Herpes, Syphilis, HPV

Question 1

What is the acute illness, residence of latency, latent illness of Herpes Simplex Virus 1, 2.
Are herpes viruses related?

Answer 1

Herpes viruses have same structure (large double stranded DNA virus) but are genetically distinct.

HSV1:

• acute: gingivo-stomatitis (gums +lips)
• latent: cold sores, encephalitis (rare)

HSV2:

• acute: Genital ulceration
• latent: genital ulcers, meningitis (rare)

NB; there is overlap between latent illness caused by HSV1 &2

Both: after infection establish latency in dorsal root of sensory ganglia.

Question 2

Compare the severity of 1’ and 2’ reactivation, the prevalence of HSV1 and 2 in NZ and the method of transmission + prevention

Answer 2

• 1’ infection is usually more severe than 2’ but 30-50% of those infected have no 1’ illness.
• HSV1 more prevalent than HSV2
• Transmission with close contact/ perinatal.
• V contagious condom use prevents heterosexual transmission (more m->w)

Question 3

What is the treatment of HSV1, 2 and Varicella-Zoster, how does it work,

Answer 3

Acyclovir (prodrug)
or
Valacylcovir - better absorbed and transformed back to acyclovir by first pass metab in liver (less bioavailability)

1. Acyclovir is taken up but infected and non-infected epithelial cells.
2. In an infected cell viral thymidine kinase (3000x more active than in non infected cells) phosphorylates acyclovir to activate it
3. Host cell thymidine kinases phosphorylate it 2 more times to make the active form AGT.
4. AGT enters the host nucleus and is incorporated into viral DNA chain which jams viral DNA polymerase and stops replication
5. Epithelial cell will die without making heaps of HPV (was going to die anyway) . Still makes ulceration

Question 4

How is HSV diagnosed and how is acyclovir used as a treatment, eg, prophylaxis

Answer 4

Diagnosis:

• mainly clinical recognition of cold sore, typical genital lesion
• confirm with swab from epithelial cells from vesicle base or vesicle fluid to PCR.

Acyclovir is used to treat
-1’ genital herpes
=1 severe 1’ oral herpes: mouth too sore to eat
-prophylaxis against recurrent genital herpes: everyday for 3-6 mo then stop, 50% fine, 50% comes back.

Question 5

What are the 4 complications of HSV - presentation and treatments if known

Answer 5

1. HSV1 Encephalitis:
   - Prodronal phase of strange behaviour
   - Fever, seizures and coma, high mortality, temporal lobe damage

Needs ICU and IV acyclovir 10mg/kg for 8 hours

2. HSV2 Meningitis: headache, neck stiffness, photophobia
   - self limiting, treatment of doubtful benefit
3. Eczema herpeticum: widespread HSV vesicles in person with ezcema
   - highly contagious
   treat with oral valacyclovir
4. severe Tissue necrosis in immunosuppressed patients.

Question 6

What is the name, microscopic appearance, transmission, and culturability of Syphilis

Answer 6

Name: Treponema Pallidum

• Spiralchete, can’t be gram stained, needs special dark field/fluorescent microscopy.
  = Can’t be cultured

-Transmitted though intercourse&raquo_space;> other.
Or in utero from infected mother.

generally unaware.

Question 7

Describe first two steps of Syphilis infection : presentation

Answer 7

1.From infection there is 21 days incubation: bacteremia to body organs

2. Primary syphilis:
   - chancre: painless papule that becomes ulcerated
   - Rubbery groin lymphadenopathy
   - Without treatment heals in 3-6 wks

Question 8

What are the possible presentations after 1’ syphilis

Answer 8

3a) Latent Syphilis:
- no current illness, history of treatment
- abnormal serology results
- reactivation more likely < 4 years post infection.

3b) Secondary Syphilis: Disseminated syphillis: symptoms/illness can occur in any organ system
- Skin involved 90% body rash + palm/soles.
- Systemic symptoms 70%: fever, lymphadenopathy, headache.
- CNS 40% (assymptomatic meningitis)
- 75% assymptomatic

Question 9

What are the possible disease after 2ndary and latent syphilis

Answer 9

Tertiary syphilis : can occur mo-years after infection, each fatal, slow death

1. Neurosyphilis:
   asymptomatic chronic meningitis: huge range of presentations, but
   - general paresis,
   - dementia,
   - tabes dorsalis- back/leg pain, ataxia, neuropathy, incontinence
2. CVS syphilis:
   endarteritis obliterans: destruction of vaso-vasorum of aorta –> hypertension and aneurysm
3. Gummatous syphilis:
   granulomatous lumps in any organ
   bone > skin > mucosa > other.

Question 10

Describe the process of diagnosing Syphilis

Answer 10

1’ is Swab of chancre visualised on dark field/fluorescent microscopy (sexual health clinic)

2’ SEROLOGY: eliza

1. enzyme immunoassay for spiralchete antigens sensitive, non specific:
   - Is syphilis even there?
   - repeat in month if - because in 1’ phase, it will not be +
2. Specific antibody test: Treponema Pallidum Particle Agglutination (TPPA)
   - Have they ever had syphilis?
3. Quantify non specific IgG, IgM antibody against Syphilis: REactive plasma reagin (RPR)
   - Do they have immune activation against syphilis right now?
   - Doubling dilutions of serum until the result is negative.

Question 11

Who should you test for syphilis

Answer 11

1. People you suspect with clinical signs/history
2. Screening of increased risk people
   - Pregnant
   - MSM, european

Question 12

Which HPV types contribute to which cancers (why) and which to warts

Answer 12

HPV16 (70%): cervical, vulval, vaginal, anal, penile, head and neck cancer.

This is because it hijacks the cell cycle, speeds it up to make more virus from cells.

HPV6, 11 to warts

Question 13

What is the structure of the Gardasil vaccine: protects against the cancer causing types + genital warts types

Answer 13

A virus like particle = empty virus shell with surface proteins from all different HPVs