Varicella-zoster virus (VZV; human herpesvirus 3) produces two clinically distinct illnesses:

Condition	Mechanism	Typical rash
Varicella/chickenpox	Primary VZV infection	Generalised, pruritic rash appearing in crops
Breakthrough varicella	Wild-type chickenpox occurring more than 42 days after vaccination	Usually milder, generalised maculopapular rash with fewer vesicles
Herpes zoster/shingles	Reactivation of latent VZV	Usually painful, unilateral and dermatomal
Disseminated zoster	Widespread reactivation, usually with significant immunocompromise	Dermatomal eruption with widespread lesions outside the primary dermatome

Chickenpox and varicella are the same condition. Shingles is not “another form of chickenpox”; it is reactivation of latent VZV following previous infection or, rarely, previous live varicella vaccination

1. Etiology & Virology

Caused by primary infection with human α-herpesvirus type 3 (Varicella-Zoster Virus, VZV).
Following primary viraemia and cutaneous replication, VZV establishes lifelong latency in dorsal-root and cranial nerve ganglia.
Reactivation (Herpes Zoster) occurs when cell-mediated immunity wanes.

2. Epidemiology

Incubation period: 10–21 days (mean ≈ 14 days).
Lifetime risk of reactivation (shingles) ≈ 30 %; increases with age (≈ 50 % by 85 years).

3. Transmission & Infectious Period

Incubation period

Usually 10–21 days after exposure.
The average is approximately 14–16 days.
The observation period may be extended to 28 days in people who receive zoster immunoglobulin.

Transmission

Chickenpox spreads through:

Airborne and respiratory secretions.
Direct contact with vesicular fluid.
Occasionally contact with contaminated articles immediately after exposure to vesicular fluid.

Localised shingles is less infectious than chickenpox. However, direct contact with shingles vesicular fluid can cause chickenpox in a susceptible contact.

Infectious period

Chickenpox:

Infectious from approximately 48 hours before rash onset.
Remains infectious until all vesicles have dried and crusted, usually around five days after rash onset.

Breakthrough varicella without vesicles:

Lesions may remain macular or papular and therefore never crust.
The person should be considered infectious until no new lesions have appeared for at least 24 hours.

Shingles:

Infectious from the onset of vesicles until all lesions have crusted, usually 7–10 days.
Airborne transmission is a particular concern with disseminated zoster or significant immunocompromise.

The period 8–21 days following exposure represents the likely incubation or surveillance period—it is not the infectious period for an asymptomatic exposed contac

4. Pathophysiology

1. Entry into the body

VZV usually enters through:

The upper respiratory tract.
The conjunctival mucosa.

The virus initially replicates within the respiratory mucosa and nearby lymphoid tissue.

2. Primary viraemia

After local replication, VZV enters the bloodstream. This initial, usually asymptomatic viraemia carries the virus to the reticuloendothelial system, including:

Regional lymph nodes.
Liver.
Spleen.

3. Secondary viral replication and viraemia

Further viral replication occurs within the reticuloendothelial system.

A secondary viraemia then distributes VZV more widely throughout the body, particularly to the skin and mucous membranes. Mild fever, malaise or other prodromal symptoms may occur during this phase.

4. Development of the chickenpox rash

VZV infects epidermal cells, causing:

Local inflammation.
Epidermal cell damage.
Formation of macules and papules.
Progression to superficial vesicles.
Subsequent pustulation and crusting.

Repeated episodes of viral spread to the skin produce lesions in successive “crops.” Consequently, macules, papules, vesicles and crusts may be present simultaneously.

5. Immune control and establishment of latency

Humoral immunity helps control circulating virus, while VZV-specific cell-mediated immunity is particularly important for limiting infection and preventing reactivation.

During the primary infection, VZV enters sensory nerve endings in the skin and travels by retrograde axonal transport to sensory nerve ganglia. The virus then establishes lifelong latency within:

Dorsal-root ganglia.
Cranial nerve ganglia.
Autonomic ganglia.

The latent virus remains within neuronal tissue without producing active clinical disease.

6. Reactivation as herpes zoster

If VZV-specific cell-mediated immunity declines, latent virus may reactivate. Factors associated with reactivation include:

Increasing age.
Immunosuppressive illness.
Immunosuppressive medication.
Malignancy or transplantation.
HIV infection.
Occasionally significant physiological stress or local trauma.

The reactivated virus replicates within the sensory ganglion and travels along the sensory nerve towards the skin by anterograde axonal transport.

This produces:

Neuropathic pain, burning, tingling or itching in the affected dermatome.
A unilateral, grouped vesicular eruption along the sensory nerve distribution.
Inflammation and damage to the sensory nerve, which may result in post-herpetic neuralgia.

In severe immunocompromise, immune containment may fail, resulting in disseminated cutaneous or visceral herpes zoster.

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5. Clinical Features

Prodrome (variable):
- fever
- malaise
- headache.
Rash:
- pruritic, polymorphic vesicles on erythematous base
- lesions in successive “crops” on scalp, face, trunk, extremities, oral mucosa.
Severity screening:
- assess for high fever
- respiratory distress
- neurological signs
- dehydration
- extensive rash (> 20 lesions)
- risk factors
  - age > 12 years unvaccinated
  - pregnancy
  - eczema
  - chronic lung disease
  - immunosuppression

6. Complications

Skin & soft tissue:
- secondary bacterial infection (GAS, S. aureus)
- necrotising fasciitis.
Respiratory:
- viral pneumonitis
- secondary bacterial pneumonia.
Neurological:
- acute cerebellar ataxia
- encephalitis
- aseptic meningitis
- Guillain–Barré syndrome.
Haematologic:
- thrombocytopenia
- purpura fulminans.
Hepatic/metabolic:
- hepatitis
- Reye syndrome (with aspirin).
Other:
- arthritis
- osteomyelitis
- glomerulonephritis
- uveitis.
Pregnancy:
- congenital varicella syndrome (≤ 20 weeks gestation)
- severe neonatal disease (maternal rash 5 days before to 2 days after delivery).
Immunocompromised:
- disseminated visceral disease (high mortality without IV aciclovir).

7. Diagnosis

Clinical: typical rash ± known exposure.
Virology (if atypical or severe):
- PCR of vesicle fluid
- serology (IgM) for retrospective confirmation.

VZV PCR

VZV nucleic-acid testing/PCR from a skin lesion is the preferred confirmatory investigation, especially in vaccinated or atypical presentations.

Preferred specimens

In descending order of expected yield:

Vesicular fluid.
Vigorous swab of the base of a freshly unroofed vesicle.
Crust or scab placed in an appropriate sterile container.
Scraping or vigorous swabbing of a maculopapular lesion when no vesicle is available.

If testing a vesicle:

Select a fresh lesion.
Unroof it with a sterile needle if required.
Firmly rotate the swab against the lesion base to collect infected epithelial cells.
Send for VZV PCR, with HSV PCR if clinically relevant.

Simply touching an intact, dry papule with a swab may provide insufficient cellular material.

Interpretation

Positive lesion VZV PCR:

Confirms VZV is present in the lesion.
In a generalised eruption, this supports varicella.
In a unilateral dermatomal eruption, this supports shingles.
PCR alone does not determine whether the clinical syndrome is chickenpox or shingles; distribution and clinical context provide that distinction.

Negative lesion VZV PCR:

Makes VZV less likely if an appropriate fresh vesicle or crust was adequately sampled.
Does not completely exclude breakthrough varicella when an early, dry, treated or non-vesicular papule was sampled.
Consider repeat PCR from a fresh vesicle or crust if new lesions appear.

If vaccination occurred 5–42 days before rash onset, a positive specimen may need referral for differentiation between wild-type and vaccine-strain VZV. Queensland Health notification criteria

Serology

VZV serology is generally less useful for diagnosing an acute rash.

VZV IgM may be insensitive or non-specific.
A single positive IgG indicates previous exposure or vaccination but does not confirm that the current rash is varicella.
Paired serology demonstrating IgG seroconversion or a substantial rise in titre may provide retrospective confirmation.
Routine testing for seroconversion after vaccination is not recommended because commercial assays may fail to detect vaccine-induced antibody levels.

8. Management

8.1 Supportive Care (Immunocompetent, < 12 years, uncomplicated)

Paracetamol for fever.
Oral antihistamines or wet wraps for pruritus.
Avoid NSAIDs and aspirin (risk of invasive GAS and Reye syndrome).
Pruritus relief →
- wet wrap dressings
- calamine/luliconazole lotion
- sedating antihistamine at night

8.2 Antiviral Therapy

Oral aciclovir
- 20 mg/kg/dose (max 800 mg) QID for 5 days if started ≤ 24 h from rash onset in high-risk but well patients (≥ 12 years unvaccinated; severe eczema; chronic lung disease; on steroids/salicylates).
IV aciclovir
- 10 mg/kg Q8 h (with renal monitoring) for severe disease, immunocompromise, neonates (< 7 days), or CNS involvement.

8.3 Secondary Bacterial Infection

Empirical anti-staphylococcal therapy (e.g. flucloxacillin ± clindamycin) guided by local antimicrobial guidelines.

9. Infection Control

Airborne + contact precautions:
- N95/P2 mask
- gown
- gloves
- eye protection.
Single-room isolation
clinic appointments – schedule at day’s end
virucidal cleaning and adequate air exchange.
Exclude non-immune staff/patients for 21 days after last exposure (28 days if VZIG received).

10. Vaccination & Post-Exposure Prophylaxis

Routine schedule (AIR):
- 1 dose MMRV at 18 months (funded)
- 2nd dose ≥ 4 weeks later (ATAGI recommends a 2nd dose ≥ 4 weeks later (but not funded))
Catch-up:
- < 14 years: 2 total doses if not vaccinated.
- ≥ 14 years/adults: 2 doses ≥ 4 weeks apart.
Post-exposure:
- live vaccine within 3–5 days (up to 7 days) for non-immune ≥ 12 months.
Zoster immunoglobulin (ZIG):
- within 96 h (≤ 10 days if supply delayed) for high-risk susceptibles (pregnant women, neonates of peripartum cases, immunocompromised).

11. Public Health & Reporting

Varicella is notifiable in all Australian jurisdictions
notify local Public Health Unit promptly.
Exclude cases from school/childcare until all lesions crusted.
Offer completion of 2-dose schedule to household contacts.

Reactivation – Herpes Zoster

1. Epidemiology & Risk Factors

Lifetime risk ≈ 30 % (≈ 1 in 3); rises to ~50 % by 85 years.
Major risk factors:
- Age-related immunosenescence (usually > 50 years)
- Immunosuppression (malignancy, HIV, transplant, corticosteroids, biologics)
- Psychological/physical stress
- Local trauma to a dermatome

2. Pathophysiology

Declining VZV-specific cell-mediated immunity permits latent virus in sensory ganglia to resume lytic replication.
Virus travels anterograde along sensory axons, causing a dermatomal vesicular eruption.
In severe immunodeficiency, visceral dissemination can occur.

3. Clinical Features

Prodrome (1–5 days): pain, tingling, itching, or burning in the affected dermatome; may have low-grade fever.
Rash: unilateral, grouped vesicles on erythematous base localized to one or adjacent dermatomes (thoracic and trigeminal most common).
Pain: often severe, can precede rash by days.

4. Complications

Complication	Key Features	At-Risk Groups
Post-herpetic neuralgia (PHN)	Persistent neuropathic pain > 90 days after rash onset; can last months to years	Older age, severe acute pain, rash extent
Ophthalmic zoster	Involvement of V1 distribution; keratitis, uveitis, optic neuritis, acute retinal necrosis	Immunocompromise, older adults
Ramsay Hunt syndrome	Geniculate ganglion involvement; vesicles in ear canal, facial palsy, hearing loss	Any age with VZV reactivation in geniculate
Neurological	Meningo-encephalitis, myelitis, cranial or peripheral motor neuropathies	Immunocompromised, older adults
VZV vasculopathy	Stroke, transient ischemic attacks	HIV, haematological malignancy
Disseminated zoster	> 20 lesions outside primary dermatome; visceral involvement (pneumonitis, hepatitis)	Severe immunosuppression
Secondary bacterial infection	Superinfection of lesions (GAS, S. aureus)	Atopic dermatitis, NSAID use, immunosuppression

5. Diagnosis

Clinical: characteristic dermatomal distribution, acute pain.
Laboratory (if atypical/severe): PCR of vesicular fluid or crusts; VZV IgM serology.

6. Management

6.1 Antiviral Therapy

Initiate within 72 hours of rash onset to reduce acute pain, lesion duration, and PHN risk.
First-line agents (oral):
- Valaciclovir 1 g TDS for 7 days
- Famciclovir 500 mg TDS for 7 days
- Aciclovir 800 mg five times daily for 7–10 days
IV aciclovir 10 mg/kg Q8 h for disseminated zoster, severe ophthalmic involvement, neurological complications, or in immunocompromised patients.

6.2 Analgesia & Symptom Control

Acute pain:
- Simple analgesics (paracetamol, NSAIDs unless contraindicated)
- Opioids for severe pain
Neuropathic pain:
- Gabapentin or pregabalin
- Tricyclic antidepressants (e.g., amitriptyline)
- Topical lidocaine patches or capsaicin cream

6.3 Adjunctive Therapies

Corticosteroids: limited evidence; may be considered in immunocompetent patients to reduce acute pain and improve quality of life, but do not prevent PHN.
Ophthalmic involvement: urgent ophthalmology referral; combine antiviral with topical steroids/antibiotics per specialist guidance.

7. Prevention

Herpes Zoster Vaccination (recommended by ATAGI):
- Zostavax (live attenuated) for 50–59 years (once only)
- Shingrix (recombinant subunit) for ≥ 50 years, two doses 2–6 months apart (preferred for immunocompetent adults)
Post-exposure prophylaxis:
- Varicella vaccination if no prior immunity and exposure to disseminated zoster

Clinical Tip: Early recognition and prompt antiviral therapy are key to reducing acute morbidity and the risk/severity of post-herpetic neuralgia. Ensure high-risk patients (elderly, immunosuppressed) are vaccinated according to current recommendations.

Vaccine “Breakthrough” Infections

No vaccine is 100 % effective. A small proportion of fully vaccinated individuals can still develop disease if exposed—so-called “breakthrough” infections.

1. Breakthrough varicella after vaccination

Breakthrough varicella is defined as wild-type varicella occurring more than 42 days after varicella vaccination.

It can occur after either one or two doses. Two doses provide substantially better protection but do not completely prevent infection.

The Australian Immunisation Handbook reports:

One-dose effectiveness of approximately 80–85% against any varicella.
One-dose effectiveness of approximately 95–98% against severe disease.
Ten-year trial protection of approximately 98.3% after two doses compared with 94.4% after one dose.

Typical breakthrough presentation

Compared with classic chickenpox, breakthrough disease usually causes:

Fewer lesions.
A generalised but less dense eruption.
Predominantly macules and papules.
Few or no obvious vesicles.
Minimal or no fever.
Minimal constitutional symptoms.
A shorter duration of illness.

The rash can still involve the trunk, back, face, arms and legs—in other words, it may still be “everywhere.”

Breakthrough varicella remains contagious. Infectivity may approach that of classic chickenpox when the patient has numerous lesions. Laboratory confirmation is strongly encouraged in vaccinated cases. Queensland Health

Distinguishing breakthrough infection from vaccine-associated rash

A mild vaccine-associated rash occurs in approximately 1–5% of recipients, typically one to three weeks after vaccination.

Consider:

Rash 5–42 days after vaccination: possible vaccine-associated eruption; strain typing may be required if VZV PCR is positive.
Rash more than 42 days after vaccination: compatible with breakthrough wild-type varicella.

2. Breakthrough Measles after vaccination

One-dose effectiveness: ≈ 96 % in Australia
Two-dose effectiveness: ≈ 99 % in Australia; one Cochrane review reports 95 % for a single dose and near-complete protection after two doses
Breakthrough measles: Very rare after two doses; most “cases” in vaccinated individuals occur with only one dose or waning immunity in adults.

Implication: Two doses confer near-complete protection; measles in a fully two-dose vaccinated person is extremely uncommon.

3. Breakthrough Mumps after vaccination

One-dose effectiveness: 60–90 % (varies by strain; Jeryl Lynn strain ≈ 69–81 %)
Two-dose effectiveness: Up to ~ 95–100 % in immunogenicity studies; real-world effectiveness ≈ 86 % (range 32–95 %)
Breakthrough mumps: More common than measles or rubella; outbreaks in highly vaccinated populations have occurred, particularly among young adults.

Implication: Even with two doses, a small percentage remain susceptible; mumps can still spread in close-contact settings, though disease tends to be milder in vaccinated individuals.

4. Breakthrough Rubella

One-dose effectiveness: ≈ 94.5–97 % against clinical rubella
Two-dose schedule: Ensures herd immunity and prevents congenital rubella; breakthrough rubella is very rare.
Breakthrough rubella: Uncommon in well-vaccinated populations; most vaccinated non-immune individuals are identified via serology before pregnancy.

Implication: Single-dose rubella vaccination protects the vast majority; two doses are recommended for women of childbearing age to maximise protection.

Key Take-Home Points

Breakthrough disease is usually milder than in unvaccinated individuals.
Two-dose schedules (for varicella and MMR) significantly enhance protection and are routinely recommended.
Ongoing surveillance and high coverage (≥ 95 %) are critical to minimise circulation and protect vulnerable groups (e.g., infants too young to be vaccinated, immunocompromised people, and pregnant women).