STD2 Flashcards
What are the features of HSV?
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
What are the epidemiological features of HSV2?
400 million cases globally- 20 mil each year
Africa is most affected
What are the structural components of HSV2?
Glycoproteins- surface
Envelope- lipid membrane
DsDNA in core- >80 + genes
Tegument- mesh of viral proteins
Capsid
What are the steps in HSV2 cell cycle?
- Binding- GC bind to receptors on cell surface
- Entry- fusion of membranes, virus is internalised into cytoplasm
- Capsid transport- accumulates in nucleus
- Transcription
- Translation
- Replication of viral genome (rolling circle)
- Capsid assembly in nucleus of affected cell
- Glycosylation- glycoproteins are translated and glycosylated into ER
- Glycoprotein export- to cell surface
- Glycoprotein containing plasma membrane endocytosis
- GC within early endosomes fuse with caspids in cytoplasm
- Virus release into ECM
How long does it take for HSV2 to cause cell lysis?
24 hours- leads to vesicle and ulcer formation
How does HSV enter sensory nerve axons?
Via plexus of free nerve ending in epidermis
-> transpired into neuronal cell bodies in dorsal root ganglia
-> replicates and spreads to other neurone
What occurs in HSV2 latency?
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
What happens upon reactivation of HSV2 in ganglia?
Transport toward genital skin or mucosa
-> replication in epidermal cells after passage of virus across axonal epithelial gap
-> discrete shedding
How long does Herpes Genitalis primary infection take to present?
4-7 days usually
-> incubation period is 2-12 days
What are the signs and symptoms of HG primary infection?
Clusters of erythematous papules/vesicles
-> painful, burning
Fever
Headache
Malaise
Myalgia
What are the features of the prodrome in recurrent lesions of HG?
Itching
Tingling
Paraesthesia
What is different about recurrent infections of HG?
Fewer lesions
Unilateral
Generally no systemic symptoms
Resolves in 3-5 days
What are the stages in HG lesion development?
Vesicle pustule
Wet ulcer
Dry crusts
How long does primary infection of HG take to resolve in absence of antivirals?
3 weeks
How long do serum antibodies for HSV2 take to appear?
12 weeks
What is a non-primary infection of HG?
Infection with HSV1 or 2 in individual that has pre-existing antibodies to other HSV
-> milder presentation due to cross-immunity
How is Herpes Genitalis diagnosed?
History
Clinical presentation
Viral diagnostic assays- viral culture, PCR for HSV DNA
Serology- HSV antibodies
-> ELISA, IMMUNOBLOT, POCkit
What are some of the differential diagnoses for HG?
Infectious
- Chancroid
- Fungal infection
- Syphilis
- Secondary bacterial infection
Non-infectious
- Aphthous ulcers
- Behcets
- Neoplasm
- Psoriasis
- Sexual trauma
Why is screening for genital herpes not advised for people with no symptoms?
False postive results
Doesn’t prompt changes in sexual behaviour
Doesn’t stop the virus from spreading
What is the aim of anti-viral therapy in Herpes Genitalis treatment?
Reduce symptoms and likelihood of transmission (no cure)
What are the regimes for people with first episodes of HG?
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
What are some of the treatment options for recurrent HG?
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
What does effective episodic treatment require?
Initiation of therapy within 1 day of lesion onset or during prodrome
When is suppressive therapy considered for HG?
If patient has six outbreaks in a year
-> reduces frequency of recurrence by 70-80%
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
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
What is the structure of HPV?
Non enveloped doubles stranded DNA virus
How is HPV spread?
Sexual contact
Microtrauma to skin or mucous membranes
How long can HPV infection remain subclinical for?
6-10 months
What conditions are associated with HPV?
Squamous Papilloma
Warts
Condyloma acuminatium
How many types of HPV are there?
Over 100
-> 40 affect anogenital areas
-> 13 are oncogenic
What do the non-oncogenic Low risk types of HPV cause? (6/11)
Genital warts
Recurrent respiratory papillomatosis
What do the oncogenic high risk types of HPV cause?
Cervical, penile, vulvar, vaginal, anal, OPG cancers
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)
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%
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
Where do anogenital warts occur in men?
Coronal sulcus
Glans
Scotrum
Penile shaft
Anal/peri-anal region
What areas doe anogenital warts typically occur in females?
External genitalia
Cervix
Anal/peri-anal area
Rare- urethra, bladder
What colour do low risk HPV lesions appear?
Variable:
Flesh coloured
Pink
Red
Brown
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
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
How long does high risk infection of HPV usually last?
12- 18 months (then cleared by immune system)
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
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
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)
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)
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
How can HPV be prevented?
Vaccine
-> given to all children aged 11-13
-> free up until age 25
