Describe the VZV virus
- dsDNA
- Enveloped
- Part of alpha herpesviridae family (like HSV)
What does primary VZV infection cause?
Chickenpox (varicella)
Where does VZV lie latent and why?
Dorsal root/cranial nerve ganglia - gets into nerve root from lesions in skin and travels to these areas
What does reactivation of VZV cause?
Shingles (zoster)
What happens during VZV reactivation?
- The virus travels down sensory nerves and produces painful vesicles in the area of skin served by the infected ganglion
- When it is travelling down the nerve it can’t be reached by T cell response
- More likely to get reactivation with T cell deficiency
What is the incubation period of varicella?
10-21 days
What symptoms occur in the prodrome of the the disease?
Fever, pharyngitis, malaise
Describe the lesions in varicella
- Itchy and painful
- Appear in crops
- Macule to papule to vesicle (blister) to pustule (yellow) to crusts
In what kind of patient is varicella more severe?
Adults and immunocompromised
What does more lesions indicate?
Higher viral load
How do you get the best sample?
Push the base of the lesion with the swab as there are more cells at the base of the lesion
What are possible complications of varicella?
1) Severe/haemorrhagic varicella
2) Pneumonia (adults)
3) Acute cerebellar ataxia (children)
4) Encephalitis
5) Secondary bacterial infection
When is someone with varicella no longer infectious?
When all the lesions have crusted over
When are you infectious with varicella?
From 48h before the rash until all lesions are crusted
Can you be asymptomatic with varicella?
Yes
Describe memory immunity of varicella
- After naturally acquired VZV infection there is persistence of VZV IgG and IgA as well as VZV CD8 and CD4 cells
- Adaptive T cell response is needed to prevent/control symptomatic reactivations of endogenous VZV (booster response when encounter someone with chickenpox)
What are the clinical features of zoster?
- Pain at site may precede eruption of painful vesicles
- Unilateral + 1-2 dermatomes involved (if immuno compromised might get multi-dermatomal shingles)
Why does an immunocompetent individual rarely suffer at most 2 attacks decades apart during a lifetime?
Bc shingles itself is a boost to VZV immunity so unlikely to get it soon after another one
What are three complications of zoster?
1) Involvement of eye in 50%, ophthalmic division of trigeminal nerve, indicated by lesion on top of nose (need to see ophthalmologist)
2) Post-herpetic neuralgia - chronic pain that continues after rash has cleared (weeks-years after) in same area as rash
3) Acute retinal necrosis PORN - can spread to both eyes and cause blindness
What does incidence of PHN increase with?
Age
What groups are more likely to get zoster?
Old and immunocompromised
What are the most common dermatomes involved?
1) Thoracic (50%)
2) Cranial (20%)
3) Trigeminal (14%)
4) Lumbosacral (16%)
When can children develop shingles?
- If they are exposed to chickenpox as a neonate due to maternal varicella infection
- They don’t develop a proper immune reaction or memory bc it is fought off by passive maternal antibodies instead of own immune system
What is a common presentation of shingles in children?
Dermatomal rash on leg
Describe zoster in the immunocompromised host
- Higher incidence
- More severe, extensive, prolonged rash
- Risk of disseminated infection 6-10 days after onset of localised rash - cutaneous, visceral, pneumonitis, hepatitis, meningoencephalitis
- More likely to get acute retinal necrosis PORN
What are the two modes of VZV transmission?
Horizontal and vertical
Describe horizontal transmission of VZV
- Respiratory route
- Starts 48h before onset of rash
- Skin lesions are infectious until crusted
Describe the two types of vertical transmission of varicella
1) Congenital infection of foetus in utero by maternal infection during pregnancy
2) Perinatal infection causing neonatal varicella
Describe congenital varicella
- Maternal varicella in the first 20 weeks of gestation results in foetal defects in <2% of cases
- Baby tends to have localised scarring, typically over joints and skin
- Rare
- Detailed check to see if mother is susceptible to varicella during pregnancy
- Give Ig if susceptible to prevent this and mainly bc mortality due to chickenpox is high during pregnancy
Describe neonatal varicella
- Maternal varicella occurring within 7 days before/after delivery is associated with high mortality of the newborn
- Severe infection bc doesn’t have ability to fight it off as mother doesn’t have antibodies yet and immune system not developed
How do you determine VZV susceptibility?
- History of chicken pox or shingles
- VZV IgG status
What are some possible treatments used as post exposure prophylaxis?
- Aciclovir
- Varivax vaccine (live - can’t use in pregnant or IC) - within 72h of exposure
- VZV IgG (VZIG) - for those at risk of severe infection after significant exposure, within 7 days, prevents or ameliorates varicella, don’t give v often
How is HSV/VZV diagnosed in skin lesions during primary or reactivated infection?
- Electron microscopy
- Immunofluorescence
- Tissue culture
- NAAT (PCR)
When is antiviral therapy for VZV used?
1) Varicella in adults and IC
2) Treatment of zoster
What does ophthalmic zoster require?
A mandatory ophthalmological assessment
What is used to treat uncomplicated childhood varicella?
Nothing
What are the first line antiviral agents for VZV (same as for HSV)?
- Aciclovir (PO/IV)
- Valaciclovir (PO)
- Famciclovir (PO)
Which is the preferential antiviral agent to use for VZV and why?
Valaciclovir bc better absorption and can use lower doses
What do antiviral agents do?
Get rid of skin lesions and symptoms but the virus is still there
What is the difference between using antiviral agents for VZV vs HSV?
VZV is less susceptible so higher doses are required
For who may the Oka varicella vaccine be recommended for in the UK?
Susceptible healthcare workers and susceptible household contacts of immunocompromised individuals (live attenuated)
For who is the zoster vaccine routinely offered?
70 and 79 year olds
Describe the zoster vaccine
- 14 x more potent than varicella vaccine
- Can’t give to someone who hasn’t had varicella
- Augments VZV specific T cell immunity
- Decreases incidence of zoster and PHN
- One dose
- Live
Describe the Oka varicella vaccine
- Live attenuated
- Blood test after may be negative bc sensitive to wild type antibodies against VZV and vaccine not so good at producing antibodies, more the T cell response
- 2 dose schedule
- May still develop chickenpox
- Protects against severe infection
- Minor vaccine associated rash
- Can be used in IC?
Describe varicella in pregnancy
- More common in women born in tropical regions bc about 50% non-immune
- Significant risk of varicella pneumonia - up to 20%, case fatality rate is high