HSV

Question 1

HSV structure & classification

Answer 1

Family: herpesviridae
Sub-family: alphaherpesvirinae
Genus: simplexvirus

unique four-layered structure: a core containing the large, ds DNA genome is enclosed by an icosapentahedral capsid which is composed of capsomers. The capsid is surrounded by an amorphous protein coat called the tegument

Baltimore: I

Question 2

HSV receptor & pathogenesis

Answer 2

Dermal keratinocytes and other epithelial sites are the principal sites of viral replication in the skin [32,33]. The virus attaches to epithelial cells through interactions between HSV-1 surface glycoproteins and cellular HSV receptors, such as nectin-1 [34], subsequently entering the cell. The virus then enters the sensory nerve ending and is transported to sensory ganglia via retrograde transport [35]. HSV-1 establishes lifelong latent infection in the trigeminal or sacral ganglia, depending on the initial site of infection. Latency is characterized by a restricted transcriptional profile, with the latency-associated transcripts (LATs) the only gene product produced

Reactivation — During the cycle of HSV recurrences, the virus undergoes reactivation from latent to lytic replication in trigeminal or sacral ganglia neurons with anterograde axonal transport to epithelial cells. The virus replicates in epithelial cells and may be shed asymptomatically or may be associated with clinically apparent ulcerations

Question 3

Specific HSV syndromes

Answer 3

1. Pharyngitis
2. Herpetic whitlow
3. Herpes gladiatorum - classically occurs on the face, neck, and arms of wrestlers. Similar to HSV in other areas, it presents initially with a vesiculopustular rash on an erythematous base that progresses to ulceration and may be misdiagnosed as folliculitis or impetigo
4. Erythema multiforme
5. Eczema herpeticum
6. Keratitis
7. Conjunctivitis & blepharitis
8. Encephalitis
9. Bell’s
10. Mollaret’s
11. RTI
12. Hepatitis
13. Oesophagitis

Question 4

HSV PCR target

Answer 4

HSV polymerase - highly conserved

Question 5

HSV treatment

Answer 5

Episode:

Aciclovir 200mg x 5 times a day for 5 days or until lesions healed

Valaciclovir 1g BD

Famciclovir

Foscarnet 40mg/kg TDS (lower dose than CMV)

Pretelivir - Pritelivir targets the helicase primase complex, which is a novel and unique target. It needs no activation by TK and thus is active against TK-resistant strains, but resistance can be selected for in culture and maps to single mutations in UL5 helicase or UL52 primase.

RECURRENCE:

1. Episodic therapy - same as above
2. Suppressive therapy - Aciclovir 400 BD - max 1 year

Question 6

Neonatal HSV transmission risk

Answer 6

Primary - 60%
First episode non primary - 25%
Recurrent - 2%

Question 7

Neonatal HSV PIER guidelines

Answer 7

1. Asymptomatic newborn + mum visible GH & labour

Vaginal delivery OR ROM> 4 hours - start IV ACV 20mg/Kg TDS while awaiting swabs (eye, throat, rectum), EDTA, CSF, AST

negative results - 10 days IV ACV - PEP
Infection - 10 days IV ACV - Pre emptive therapy
Disease - 3 weeks IV ACV + 6 months oral suppression in CNS/disseminated disease

2. Asymptomatic baby + mum recurrent GH

Extreme PREM
ROM> 4 hours
Skin damage with electrodes

Treatment same as above

Question 8

HSV resistance

Answer 8

1. Decreased production of viral TK
2. Complete deficiency in viral TK activity
3. Viral TK protein with altered substrate activity

Mutations in UL23 (phosphorylation gene) and UL30 (DNA polymerase gene).

Question 9

New HSV agents

Answer 9

Amenamevir & Pretelivir: Helicase primase inhibitors (UL5 & UL52 regions)

Question 10

HSV keratitis treatment

Answer 10

1. Acyclovir gel
2. Ganciclovir ointment
3. Trifluridine

Question 11

HSV encephalitis management

Answer 11

CSF positive for HSV:
14 days IV acyclovir in Immunocompetent
21 days IV aciovir in immunocompromised

Re-LP at 14/21 days and if PCR positive, 7 more days IV acyclovir + re-LP

Aciclovir: 10mg/Kg TDS

Question 12

HSV in 3rd trimester

Answer 12

Primary HSV

• Standard doses of aciclovir (usually PO, IV if disseminated)
• Continue daily suppressive aciclovir 400 mg TDS until delivery
• Recommend caesarean, particularly if episode is within 6 weeks of expected delivery
• Type-specific HSV antibody (IgG) testing is advisable to distinguish between primary and recurrent genital HSV infections

Recurrent genital herpes

• Recurrences usually resolve within 7-10 days without antiviral treatment
• Vaginal delivery should be anticipated
• Consider daily suppressive aciclovir 400 mg TDS from 36 weeks

Question 13

Primary HSV at onset of labour

Answer 13

•Recommend caesarean to all women presenting with primary episode genital herpes lesions at the time of delivery, or within 6 weeks expected delivery date
• Benefits of caesarean may reduce if the membranes have been ruptured > 4 hours - however, there may be some benefit even after this time interval
• Consider intrapartum IV aciclovir for the mother (5 mg/kg 8 hourly) and the neonate (20 mg/kg 8 hourly) if opting for vaginal delivery
• Although vaginal delivery should be avoided if possible, in women who deliver vaginally in the presence of primary genital herpes lesions, avoid invasive procedures

Question 14

HSV incubation

Answer 14

2-14 days

Question 15

HSV diagnostics

Answer 15

RT-PCR
Serology

Western blot - Gold standard