Chickenpox (Varicella)

1. Causative Organism
2. Clinical Signs Symptoms and Complications
3. Method of Transmission
4. Public Health Significance
5. Prevention - Non Immunisation Methods
6. Prevention - Immunisation
7. Vaccine/s and Vaccination
8. Efficacy and Effectiveness
9. Availability
10. Dosage and Administration
11. Indications and Recommendations
12. Adverse Events
13. Contraidications
14. Risks vs Benefits

Causative Organism

Human herpes virus type 3 (Varicella Zoster virus)

Signs, Symptoms and Complications

• Fever and/or general unwellness for a day or two
• This is followed by a rash, which starts out as small pimples and changes to blisters with a red base. The rash usually starts on the head, then the trunk and then moves to the limbs. Lesions may also be found in the mouth and vagina.
• Varicella is usually, but not always, a mild disease of 1 – 2 weeks duration in healthy children.
• It is more severe in adults and can cause serious, and even fatal, illness in immunosuppressed subjects of any age.
• Complications include cerebellitis, aseptic meningitis, transverse myelitis, thrombocytopenia, pneumonia, mesenteric adenitis and arthralgia or arthritis.
• About two-thirds of the complications occur in otherwise healthy children, and less than one-tenth in children with a disease associated with immune-suppression
• Varicella symptoms may be more severe for adolescents and adults, those with skin conditions or recent sunburn, lung conditions, e.g. smokers or those with asthma and those who have recently taken steroids.
• Where a pregnant, non-immune woman has varicella in weeks 8-20 of pregnancy, there is a 0.7-2% chance of Congenital Varicella Syndrome, which may include: scars, partial or complete blindness, poor growth, limb malformations, cranial malformations, delayed development, mental retardation, spontaneous abortion or foetal death.
• There is a high risk (17-30%) of serious disease for the infant if the mother has chickenpox between the 5th day before delivery and two days afterwards. 
• Herpes zoster (shingles) is due to reactivation of latent varicella virus infection. This consists of a dermatomally distributed vesicular rash. The majority of cases of zoster occur in adults over 40 yrs of age and in immune-suppressed individuals. Opthalmic herpes zoster may cause permanent loss of vision.
• Infants exposed to varicella in-utero between 25 and 36 weeks gestation have a 0.8-1.7% risk of developing herpes zoster in infancy.
  Super infection with group A beta-haemolytic streptococci occurs and can be fatal.

Method of Transmission

• Varicella is highly contagious and spread by droplet infection (coughing and sneezing) or by direct contact with weeping blisters.
• Transmission of the virus is less efficient in tropical climates, probably reflecting the extreme thermolability of this virus.

Public Health Significance

• An estimated 90% of all children are infected with varicella before they reach adolescence.
• Adults, adolescents and those with immuno-suppression are more likely to experience serious disease.
• Varicella is highly infectious, from up to 2 days before appearance of the rash until blisters have crusted (usually about 5-7 days after the appearance of the rash). If one person has chickenpox, about 85% of their close contacts will get it too, unless they have had the disease or the relevant vaccine.
• Babies born to women who contract varicella in the first 2 trimesters of pregnancy have a 0.7-2% chance of congenital varicella syndrome.
• Babies whose mother has onset of chicken pox from 5 days before until 2 days after delivery have a 17-30% of developing severe disease. The elderly and the immuno-compromised may develop herpes zoster due to reactivation of latent varicella virus. There is a 50% chance of developing shingles between the ages of 50 and 65 in the USA.
• The risks of severe complications from super infection with group A beta-haemolytic streptococci, (including cellulitis, streptococcal toxic shock syndrome, necrotising fasciitis and post-infectious glomerulonephritis), is of concern due to the continued resurgence of highly virulent strains of Streptococcus pyogenes since the early 1980s, particularly in countries with developed economies.

New Zealand Epidemiology

• In New Zealand it is expected that 90 percent of children would have had varicella infection before adolescence, with peak incidence in the five to nine years age group.
• With higher participation rates in preschool education, a greater proportion of infections may now be occurring in preschool aged children.
• Hospitalisation: Only 4 percent of hospitalisations involved people with an underlying disease associated with immune suppression. The rate of hospital discharges for the zero to four and five to nine years age groups was higher compared with older age groups because the disease is most common in childhood. However, adults, adolescents and infants are more likely to suffer severe illness or the complications of chickenpox.
• Based on overseas rates, it is estimated that up to one case of congenital varicella syndrome may be expected in New Zealand each year, although few have been reported.
• Mortality: Mortality data are available for the period 1980 to 2002. Nine deaths were attributed to chickenpox over the 14-year period 1980 to 1993, of which four occurred in children, two in infants and three in adolescents or adults.
•  None of the cases who died had a contributory cause of death recorded.
• From 1994 to 2002 there were nine deaths associated with varicella, two were children aged five to nine years, four were adults aged 30 to 64 years and three were adults over the age of 65 years.
• Larger series from other developed temperate climate countries suggest that up to 10 percent of chickenpox deaths may involve individuals with immune suppression.

In summary, in a typical year New Zealand is estimated to experience approximately 50,000 chickenpox infections, of which 150–200 result in hospitalisation, one to two cases result in residual long term disability or death, and 0.5–1 cases result in severe congenital varicella syndrome. About two-thirds of this burden is borne by otherwise healthy children, and less than one-tenth by children with a disease associated with immune suppression.

From New Zealand Immunisation Handbook 2006 [Click Here] for PDF of Varicella Chapter.

Prevention - Non-Immunisation Related

• Varicella virus is airborne and highly contagious before the rash appears, so is difficult to avoid.
• Parents/caregivers should exclude cases from early childhood services or school until fully recovered and all lesions have crusted.
• High risk contacts should also be excluded from early childhood services and school during the duration of an outbreak.
• Anti-viral medication (acyclovir or guancylovir) may be important for these groups, as well as for individuals in the same household, who subsequently contract varicella due to increased risk of transmission of the virus.
• Passive Immunisation - Post-exposure prophylaxis with Zoster Immune Globulin (ZIG) - this is also effective if given within 72 hours of exposure and possibly up to 7 days. The recommended concentration is 100 U/mL, dosage 6mL for adults, 4mL for children aged 6-12y and 2mL for children aged 0-5 years old. Large doses of normal IG are indicated when ZIG is unavailable. 
• Candidates for ZIG (who have been exposed and are likely to be susceptible) include:
  • Immune-compromised individuals
  • Pregnant women
  • Newborn infants whose mother had onset of chickenpox within 7 days before or after delivery.
  • Hospitalised premature infants whose mothers have no history of chickenpox or are less than 28 weeks gestation at birth or under 1000g in weight, regardless of the mother’s chickenpox history.
  • Asymptomatic HIV positive individuals.
• Contact can be defined as:
  • Household contact – individuals living in the same house are very likely to be infected if susceptible.
  • Play mate contact – defined as more than one hour of play indoors with an infected individual.
  • Newborn infant contact – occurs when the mother of a newborn infant develops chickenpox, but not shingles, from one week before to one week after delivery.
    

Prevention - Vaccination

• Currently-available vaccines are based on the attenuated Oka strain developed in Japan. 
• These are grown on Human MR5 diploid cells.
• The final vaccine contains a lyophilised purified viral extract - contains trace residues of MR5 cell material. This is reconstituted with 0.5 mL of buffer solution (a phosphate-based buffer with gelatin). 
• Varicella vaccines also contain trace amounts of neomycin.
• The manufacturer of Varilrix (GSK) have recently changed their dose recommendation for children aged 9 months to 13 years. They now recommended two doses of Varilrix six weeks apart to provide optimal protection for this age group. This is reasonable, however, New Zealand has a lot of circulating wild varicella virus, children are highly likely to receive boosts to their immunity from contact with wild disease, and a single dose of vaccine is likely to be effective. Where break through disease occurs, chicken pox in a previously vaccinated child, it is usually mild. Parents should be provided with the above information so as to be able to balance the potential benefit of a second chicken pox vaccination against the cost.
• The advice for Varivax (MSD) remains the same. A single dose of Varivax is recommended for children aged 12 months to 13 years.
• A tetravalent mumps-measles-rubella-varicella (MMRV) vaccine is now licensed, but not yet available in New Zealand. It may be used in place of the second MMR vaccination at 4 years of age in countries where it is available. 
• Zostavax^®, a vaccine for prevention of herpes zoster and postherpetic neuralgia in older adults is also now licensed, but not available outside of the U.S.A.

Efficacy and Effectiveness

• More than 20 years after immunisation, studies in Japan suggest long-lasting immunity.
• Seroconversion occurs in 90-100% of those vaccinated and about 70 to 90% are protected when exposed to infection within the household.
• Breakthrough infection after exposure in those vaccinated is usually mild.
• The protective efficacy against the development of shingles is about 60% for the higher dose vaccine.
• Zostavax® is licensed but only available within the U.S.A. It has been shown to reduce morbidity from herpes zoster (shingles) by 61.1% and 66.5% respectively. 
• Initially in the U.S. a single varicella vaccination was part of the national immunisation programme. The vaccine effectiveness meant much less wild disease was circulating and subsequently less immunity boosting occurred. Adolescents in the U.S. began experiencing breakthrough varicella disease and the U.S. introduced a two dose varicella vaccination schedule for children. Australia, who also have a single varicella vaccination on their national immunisation programme, may be following a similar trend of reduced incidence of wild varicella disease. In New Zealand the varicella vaccine is not on the National Immunisation Schedule, we are not experiencing a reduction in wild varicella disease.

Availability

• Universal varicella immunisation is not currently recommended by the WHO. 
• Varicella is now on the national immunisation programme for several countries including Australia and the U.S.A.
• Varicella vaccines are available for purchase in most countries. 
• Currently, both VARILRIX^® and VARIVAX^® (both based on the Oka strain) are licensed and are available in New Zealand for private purchase.
• Zostavax® is not currently available in New Zealand.

Measles, mumps, rubella and varicella vaccine (MMRV)

• In the U.S. a MMRV vaccine (ProQuad^®, Merck) that is freezer stable is now licensed. Thevaccine is not available in New Zealand.
• There is also a refrigerator stable two-dose MMRV vaccine (GSK) recommended for use in place of the second MMR vaccination at 4 years of age. It is not currently available in New Zealand.  

Dosage and Administration

• Children (aged 9 months to 13 years) – a single 0.5 mL dose.
• The manufacturer of Varilrix (GSK) have recently changed their dose recommendation for children aged 9 months up to 13 years. They now recommended two doses of Varilrix six weeks apart to provide optimal protection for this age group. This is a reasonable, however, New Zealand has a lot of circulating wild varicella virus, children are highly likely to receive boosts to their immunity from contact with wild disease, and a single dose of vaccine is likely to be effective. Where break through disease occurs, chicken pox in a previously vaccinated child, it is usually mild. Parents and caregivers should be advised to balance the potential benefit of a second chicken pox vaccination against the cost.
• Adolescents and adults (14 years of age and older) – Two 0.5 mL doses, administered four to eight weeks apart.
• Varicella vaccination should be administered by SC injection, preferably into the upper arm (deltoid region).
• The vaccine can be given at the same time as other vaccines, including MMR, DTaP, hepatitis B and meningococcal C conjugate vaccine, using separate syringes and injection sites, without decreasing immunogenicity or increasing reactogenicity.
• If varicella vaccine is not given simultaneously with other live virus vaccines, e.g. MMR, it should be given at least 4 weeks apart.

Indications and recommendations

• Varicella immunisation can be considered for:
• Children aged 9 months to 13 years of age. Unless they have already suffered chickenpox.
• Susceptible (no history of Chickenpox) persons aged 14 years and older – The vaccine is especially indicated for those in the following categories:
  • Susceptible Individuals  in high-risk occupations, such as health-care workers (particularly those working in obstetric, neonatal or pediatric units or those caring for immuno-suppressed children or infants, teachers and workers in childcare centres).
  • Susceptible women, prior to pregnancy.
  • Susceptible parents and adolescent household contacts of young children.
  • Susceptible household contacts, (adults and children over 18 months), of immuno-suppressed persons.

Other Considerations

• Serology Persons aged 14 years or older who have a reliable history of varicella should be considered immune.
• Serological testing before vaccination can be considered where feasible, for both adults and adolescents with a negative history of varicella-zoster disease, as 61% without a clear history of varicella are immune. Adolescents and adults can be vaccinated without testing, provided there are no contraindications, as the vaccine is well-tolerated in seropositive persons.
• “Ring-fence” protection. If an immune-suppressed individual cannot be immunised, non-immune household members and other close contacts should be immunised. Vaccine strain virus transmission is extremely rare and if it does occur is likely to cause mild disease compared with the relatively high risk of exposure to wild type varicella-zoster virus. If vaccinees develop a rash, they should avoid contact with immuno-compromised persons for the duration of the rash. ZIG is not required for such immuno-compromised individuals, as the disease associated with this type of transmission, should it occur, would be expected to be mild.
• A Health Care Worker (HCW) with a negative or uncertain history of varicella can be serologically tested. If found to be negative, vaccination should be offered. If a rash develops during the 6 weeks following vaccination, the HCW should be re-assigned to duties that require no patient contact or placed on sick leave until the rash clears. The rash resulting from vaccination may be atypical, may not be vesicular and is likely to last for less than one week.
• Post exposure prophylaxis. Vaccination may be effective if given to an individual within 3 and up to 5 days after exposure. If a health care worker exposed to varicella is unimmunised or has a negative or uncertain history of varicella, offer vaccination. In situations where facilities for a rapid serotest are available, it may be possible to test prior to vaccination to identify those with pre-existing immunity. Vaccination should not be delayed beyond the recommended 3 to 5 days after exposure. Vaccination in the absence of serological results can be safely carried out (provided there are no other contraindications). IHCWs who are not vaccinated could be re-assigned duties or placed on sick leave beginning 10 days after exposure and ending 21 days after exposure.
• Persons who live or work in environments where transmission may occur readily. These include tertiary students, inmates and staff of correctional institutions and armed forces personnel. If a rapid serotest is available and feasible, it may be possible to identify those with pre-existing immunity prior to vaccination.
• International travellers. The Advisory Committee on Immunisation Practice in the USA recommends vaccination of all non-immune individuals before commencing any type of international travel.

Contraindications

• Persons with previous anaphylactic reaction to:
  • Gelatin or Neomycin
  • A previous dose of varicella vaccine
• Pregnancy.
• Persons with primary or acquired immune-deficiency, including children with immune-suppression secondary to HIV or AIDS.
• Persons on high dose steroids for 14 days or longer, e.g. >2mg/kg/day of prednisone or its equivalent or >20mg per day, if their weight is over 10kg.
• Persons who have received a dose of another live vaccine within the previous 4 weeks.  Other live vaccines may be given concurrently with varicella vaccine.
  

The following should seek specialist advice before vaccination with varicella vaccine:

• People who live with a household member who is immuno-compromised and not immune to chickenpox.
• Those with HIV/AIDS or any disease that affects the immune system.
• Those being treated with drugs that affect the immune system, e.g. high dose steroids.
• Those with any kind of neoplastic disease.
• Those undergoing radiotherapy or chemotherapy for cancer.
• Those who have recently had a transfusion or have been given other blood products.
  

Reactogenicity and Adverse Events

• Fever (1:10 or less)
• Mild rash (1:20 or less) - very rarely infectious
• Seizure caused by fever (1:1,000 or less)
• Pain and/or swelling at injection site is not uncommon (1:5 children, 1:3 adults).
• No serious adverse events were reported from pre-licensure trials.
• Post-licensure, serious adverse events have been reported to be temporally related to vaccination at a rate of 2.9 per 100 000 doses distributed. These include encephalitis, ataxia, erythema multiforme, pneumonia, thrombocytopenia, seizures, neuropathy, anaphylaxis and death.
• A causal relationship between varicella vaccine and these events has not been determined, although such a causal link is plausible for anaphylaxis and for thrombocytopenia, ataxia and encephalitis, as the latter are rare complications of natural varicella infection.
  

Risks of Disease vs. Risks from vaccine

Disease	Effects of Disease	Side Effects of Vaccine
Varicella (chickenpox) - caused by highly contagious virus, causes low-grade fever and vescicular rash, which sometimes leaves scars. Reactivation of the virus late in life causes herpes zoster (shingles).	1 in 5000 develop encephalitis (brain inflammation) About 2 in 500,000 patients die or suffer permanent disability. Infection during pregnancy can result in congenital malformations in the baby (1-2 per 100). Onset of infection in the mother from 5 days before to 2 days after delivery results in severe infection in the newborn baby in up to one third of cases. Herpes zoster causes severe pain often prolonged and disabling.	About 1 in 5 has a local reaction or fever. 1 in 10,000 may have a febrile seizure. A mild varicella-like rash may develop in 3-5 per 100 recipients. Mild local reactions.

Click the link to view the PDF file in your browser. Or right-click (Mac users click and hold) and choose 'save target as' to save the file to disk for offline viewing. Adobe Reader X is required to view the resources - download here.