HSV Flashcards
HSV structure & classification
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
HSV receptor & pathogenesis
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
Specific HSV syndromes
- Pharyngitis
- Herpetic whitlow
- 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
- Erythema multiforme
- Eczema herpeticum
- Keratitis
- Conjunctivitis & blepharitis
- Encephalitis
- Bell’s
- Mollaret’s
- RTI
- Hepatitis
- Oesophagitis
HSV PCR target
HSV polymerase - highly conserved
HSV treatment
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:
- Episodic therapy - same as above
- Suppressive therapy - Aciclovir 400 BD - max 1 year
Neonatal HSV transmission risk
Primary - 60%
First episode non primary - 25%
Recurrent - 2%
Neonatal HSV PIER guidelines
- 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
- Asymptomatic baby + mum recurrent GH
Extreme PREM
ROM> 4 hours
Skin damage with electrodes
Treatment same as above
HSV resistance
- Decreased production of viral TK
- Complete deficiency in viral TK activity
- Viral TK protein with altered substrate activity
Mutations in UL23 (phosphorylation gene) and UL30 (DNA polymerase gene).
New HSV agents
Amenamevir & Pretelivir: Helicase primase inhibitors (UL5 & UL52 regions)
HSV keratitis treatment
- Acyclovir gel
- Ganciclovir ointment
- Trifluridine
HSV encephalitis management
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
HSV in 3rd trimester
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
Primary HSV at onset of labour
•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
HSV incubation
2-14 days
HSV diagnostics
RT-PCR
Serology
Western blot - Gold standard
