STD2 Flashcards

1
Q

What are the features of HSV?

A

Double stranded DNA virus

Part of alpha-herpesviridae family

HSV1- oral vesicular lesions (may be responsible for genital lesions in young adults)

HSV2- genital vesicular lesions

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2
Q

What are the epidemiological features of HSV2?

A

400 million cases globally- 20 mil each year

Africa is most affected

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3
Q

What are the structural components of HSV2?

A

Glycoproteins- surface

Envelope- lipid membrane

DsDNA in core- >80 + genes

Tegument- mesh of viral proteins

Capsid

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4
Q

What are the steps in HSV2 cell cycle?

A
  1. Binding- GC bind to receptors on cell surface
  2. Entry- fusion of membranes, virus is internalised into cytoplasm
  3. Capsid transport- accumulates in nucleus
  4. Transcription
  5. Translation
  6. Replication of viral genome (rolling circle)
  7. Capsid assembly in nucleus of affected cell
  8. Glycosylation- glycoproteins are translated and glycosylated into ER
  9. Glycoprotein export- to cell surface
  10. Glycoprotein containing plasma membrane endocytosis
  11. GC within early endosomes fuse with caspids in cytoplasm
  12. Virus release into ECM
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5
Q

How long does it take for HSV2 to cause cell lysis?

A

24 hours- leads to vesicle and ulcer formation

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6
Q

How does HSV enter sensory nerve axons?

A

Via plexus of free nerve ending in epidermis
-> transpired into neuronal cell bodies in dorsal root ganglia
-> replicates and spreads to other neurone

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7
Q

What occurs in HSV2 latency?

A

Viral genome is maintained within ganglia for life of host as circular genetic elements called episomes in the nucleus
-> closely associated but not integrated into host DNA

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8
Q

What happens upon reactivation of HSV2 in ganglia?

A

Transport toward genital skin or mucosa
-> replication in epidermal cells after passage of virus across axonal epithelial gap
-> discrete shedding

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9
Q

How long does Herpes Genitalis primary infection take to present?

A

4-7 days usually
-> incubation period is 2-12 days

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10
Q

What are the signs and symptoms of HG primary infection?

A

Clusters of erythematous papules/vesicles
-> painful, burning

Fever

Headache

Malaise

Myalgia

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11
Q

What are the features of the prodrome in recurrent lesions of HG?

A

Itching

Tingling

Paraesthesia

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12
Q

What is different about recurrent infections of HG?

A

Fewer lesions

Unilateral

Generally no systemic symptoms

Resolves in 3-5 days

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13
Q

What are the stages in HG lesion development?

A

Vesicle pustule

Wet ulcer

Dry crusts

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14
Q

How long does primary infection of HG take to resolve in absence of antivirals?

A

3 weeks

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15
Q

How long do serum antibodies for HSV2 take to appear?

A

12 weeks

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16
Q

What is a non-primary infection of HG?

A

Infection with HSV1 or 2 in individual that has pre-existing antibodies to other HSV
-> milder presentation due to cross-immunity

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17
Q

How is Herpes Genitalis diagnosed?

A

History

Clinical presentation

Viral diagnostic assays- viral culture, PCR for HSV DNA

Serology- HSV antibodies
-> ELISA, IMMUNOBLOT, POCkit

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18
Q

What are some of the differential diagnoses for HG?

A

Infectious
- Chancroid
- Fungal infection
- Syphilis
- Secondary bacterial infection

Non-infectious
- Aphthous ulcers
- Behcets
- Neoplasm
- Psoriasis
- Sexual trauma

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19
Q

Why is screening for genital herpes not advised for people with no symptoms?

A

False postive results

Doesn’t prompt changes in sexual behaviour

Doesn’t stop the virus from spreading

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20
Q

What is the aim of anti-viral therapy in Herpes Genitalis treatment?

A

Reduce symptoms and likelihood of transmission (no cure)

21
Q

What are the regimes for people with first episodes of HG?

A

Acyclovir- 400mg x 3 per day for 7-10 days

Acyclovir- 200mg x 5 per day for 7-10 days

Valacyclovir- 1g x 2 per day for 7-10 days

Famciclovir- 250mg x 3 per day for 7-10 days

22
Q

What are some of the treatment options for recurrent HG?

A

Acyclovir- 400mg x 3 per day for 5 days OR 800mg x2 per day for 5 days

Famciclovir- 125mg x 2 per day for 5 days

23
Q

What does effective episodic treatment require?

A

Initiation of therapy within 1 day of lesion onset or during prodrome

24
Q

When is suppressive therapy considered for HG?

A

If patient has six outbreaks in a year
-> reduces frequency of recurrence by 70-80%

25
What are the treatment options for suppressive therapy of HSV?
Acyclovir- 400mg x 2 per day Famciclovir- 250mg x2 per day Valacyclovir- 1g x 2 per day
26
What are the risk factors for HG?
Increased number of lifetime sex partners Oral-genital contact Presence of other sexual transmitted diseases Female sex OCP use Black/non-hispanic race
27
What is the structure of HPV?
Non enveloped doubles stranded DNA virus
28
How is HPV spread?
Sexual contact Microtrauma to skin or mucous membranes
29
How long can HPV infection remain subclinical for?
6-10 months
30
What conditions are associated with HPV?
Squamous Papilloma Warts Condyloma acuminatium
31
How many types of HPV are there?
Over 100 -> 40 affect anogenital areas -> 13 are oncogenic
32
What do the non-oncogenic Low risk types of HPV cause? (6/11)
Genital warts Recurrent respiratory papillomatosis
33
What do the oncogenic high risk types of HPV cause?
Cervical, penile, vulvar, vaginal, anal, OPG cancers
34
What allows oncogenic HPV to drive cell division in neoplasia?
Ability of E7 protein to bind and degrade pRb proteins Ability of E6 to degrade P53 and compromise PDZ-domain proteins (regulate cell contact and signalling)
35
What are the top 5 most prevalent types of HPV?
HPV16- 3.2% HPV18- 1.4% HPV52- 0.9% HPV31- 0.8% HPV58- 0.7%
36
How does anogenital warts/condyloma acuminata present?
Exophytic lesions -> Sessile/pendunculated -> single, multiple, multifocal Begin as small discrete, soft, pearly papules that coalesce into a plaque over time -> Can also be verrocous, hyperkeratotic, fungating
37
Where do anogenital warts occur in men?
Coronal sulcus Glans Scotrum Penile shaft Anal/peri-anal region
38
What areas doe anogenital warts typically occur in females?
External genitalia Cervix Anal/peri-anal area Rare- urethra, bladder
39
What colour do low risk HPV lesions appear?
Variable: Flesh coloured Pink Red Brown
40
What are the histological features of HPV genital warts?
Elongation of dermal papillae Hyperplasia of stratum spinosum (acanthosis) Large vacuolated cells (koilocytes) in stratum granulosum
41
What are the oral lesions that HPV can cause?
Verruca vulgaris (common wart): exophytic upside down V surface Condyloma acuminatum: exophytic cauliflower-like surface (sideways C) Squamous Papilloma: exophytic hairy-like (pedunculated- P shaped) lesions
42
How long does high risk infection of HPV usually last?
12- 18 months (then cleared by immune system)
43
What hap[pens if host immune system fails to clear HPV 16/18 infection?
Protein E2- which is negative regulator of E6/7 gets abrogated -> over expression of E6/7 which results in inhibition of tumour suppressor proteins
44
What does inhibition of tumour suppressor genes by E6/7 cause?
Inhibition of interferon response Activation of telomerase Promotion of cell divisions Immortalisation and transformation -> genetic instability, unregulated replication, accumulation of aberrant chromosomal mutations, dysplasia
45
What occurs in a high risk silent infection?
Viral genomes persist in basal layer without development of disease or can lead to precancerous squamous intraepithelial neoplasias (cervical, vulval, vaginal, penile, anal)
46
How is HPV diagnoses?
Clinical appearance Hsitology- koliocytes HPV-DNA on PCR Serology- not suitable for distinguishing between acute and prior infections (weak immune response)
47
What treatments are available for HPV?
Podofilox- wart necrosis -> BID for 3 days consecutively per week for 4 weeks Imiquimod 3.75-5% cream Sinecatechins 10-15% ointment Surgical excision Cryotherapy
48
How can HPV be prevented?
Vaccine -> given to all children aged 11-13 -> free up until age 25