Varicella (Chickenpox)

Description

Varicella (chickenpox) is the primary infection with the varicella-zoster virus (VZV). It is a highly contagious rash illness transmitted by airborne or droplet pathways. The usual incubation period is 14-16 days (range 10-21 days). Second cases of varicella have been reported in immunocompetent persons but are rare. Following varicella, VZV establishes latency in sensory nerve ganglia. The virus can reactivate later in life causing herpes zoster (shingles), usually localized to one to three dermatomes. Transmission of VZV to a susceptible person occurs through contact with either a person with varicella or, less commonly, a person with herpes zoster.

Varicella is generally a mild disease in children. It usually lasts 4-7 days and is characterised by a short (1- to 2-day) or absent prodromal period (low-grade fever, malaise) and by a pruritic rash consisting of crops of macules, papules, vesicles, and eventual crusting, which appear in three or more successive waves. Serious complications are the exception but can occur mainly in infants, adolescents, adults, and immunocompromised persons. They include secondary bacterial infections of skin lesions, pneumonia, cerebellar ataxia, and encephalitis. Because the vaccine is 70%-90% effective, a modified varicella, known as breakthrough disease, can occur in some vaccinated persons. Breakthrough disease is almost always mild with rash with fewer than 50 skin lesions, which may be atypical in appearance.

Occurrence

Before introduction of varicella vaccine in the United States in 1995, varicella was endemic with virtually all persons being infected by adulthood. Since implementation of the varicella vaccination programme, incidence has declined in all age groups, with the greatest decline among children aged 1-4 years. Data from passive and active surveillance have indicated a decline in varicella cases of 70%-84% between 1995 and 2001, in areas with vaccine coverage of 73%-84% among children aged 19-35 months.

Risk for Travellers

Varicella and herpes zoster occur worldwide, but varicella vaccine is routinely used for vaccination of children in only few countries such as the United States, Uruguay, and Quatar. The risk of varicella infection for travellers coming to the United States is lower than for travel anywhere else in the world. However, VZV is still widely circulating in the United States. Additionally, exposure to herpes zoster, while less common than varicella, poses a risk for varicella infection. In temperate climates, in the absence of vaccination, most of varicella cases are reported among preschool and school-aged children during winter and spring. Data suggest that in tropical areas VZV infection occurs more commonly among adults than among children. Reasons for this difference in disease epidemiology are unclear. They may relate to the agent's heat lability and/or to factors such as the tendency for less indoor crowding in tropical regions.

Prevention

Varicella vaccine contains live, attenuated VZV. It is currently available only as a single-antigen formulation. Varicella vaccine is recommended for routine immunisation of all children without contraindications at 12-18 months of age and for susceptible older children, adolescents, and adults. Those who have a reliable or uncertain history of varicella are considered susceptible. Children 1-12 years of age should receive one dose of vaccine. Persons 13 years of age should receive two doses, 4-8 weeks apart. The vaccine should be administered routinely to children 12-18 months of age, regardless of their prior history of varicella. Children 19 months of age, adolescents, and adults with reliable parental or personal histories of varicella are considered immune and do not need to be vaccinated. Epidemiologic and serologic studies indicated that >95% of American adults are immune to varicella. In addition, 71%-93% of adults without a reliable history of varicella are actually immune. As a result, serologic testing prior to vaccination is likely to be cost effective for adults. In case of uncertainty, prior varicella disease is not a contraindication to varicella vaccination. Although vaccination against varicella is not a requirement for entry into any country (including the United States), persons travelling or living abroad should ensure that they are immune.

After one dose of varicella vaccine, 97% of children 1-12 years of age develop detectable antibody titers. Vaccine-induced immunity is believed to be long lasting. Vaccine efficacy is estimated to be 70%-90% against disease of any severity and 95% against severe disease. Among healthy adolescents and adults, an average of 78% develop antibody after one dose and 99% develop antibody after a second dose administered 4-8 weeks later.

Varicella vaccine may be administered simultaneously (but at a different site) with any other live or inactivated vaccine. Inactivated vaccines and typhoid vaccines may be administered at any time before or after varicella vaccine. However, if varicella vaccine or live MMR and yellow fever vaccines are not administered simultaneously, their administration should be separated by an interval of at least 28 days. (See Table 1-2 for more details.)

Adverse Reactions

The most common adverse reactions following varicella vaccine are injection site complaints such as pain, soreness, redness, and swelling that are self-limited. Fever occurs in 15% of children and 10% of adolescents and adults. A macular or accine rash usually consisting of a few lesions at the injection site is reported in 3% of children and 1% of adolescents and adults after the second dose. A generalised rash with a small number of lesions may rarely occur as well within 3 weeks of vaccination.

Varicella vaccine is a live virus vaccine and results in a latent infection similar to that caused by wild VZV. Consequently, zoster caused by the vaccine virus has been reported, but appears to occur at a much lower rate than following natural infection. Not all reported cases have been confirmed as having been caused by vaccine virus; many were caused by the wild virus.

Precautions and Contraindications

Allergy

Persons with severe allergy (hives, swelling of the mouth or throat, difficulty breathing, hypotension, and shock) to gelatin or neomycin or who have had a severe allergic reaction to a prior dose should not be vaccinated with varicella vaccine. Varicella vaccine does not contain egg protein or preservative.

Pregnancy

Women known to be pregnant or who are attempting to become pregnant should not receive varicella vaccine. The effects of varicella vaccine on a developing foetus are unknown. Because infection with wild VZV poses only a small risk to the foetus and the vaccine virus is attenuated, the risk to the foetus, if any, should be even lower than from wild VZV. Although the manufacturer's package insert recommends avoiding pregnancy for 3 months following receipt of varicella vaccine, the Advisory Committee on Immunisation Practices (ACIP) and the American Academy of Paediatrics (AAP) recommend that pregnancy be avoided for 1 month. Breastfeeding is not a contraindication to the varicella vaccination of either a woman or an infant.

Immunosuppression

Persons with immunosuppression of cellular immune function resulting from leukemia, lymphomas of any type, generalised malignancy, immunodeficiency disease, or immunosuppressive therapy should not be vaccinated. However, vaccine is available to any physician free of charge from the manufacturer through a research protocol for use in patients with leukemia in remission who meet certain eligibility criteria. Treatment with low-dose prednisone (e.g., <2 mg/kg of body weight/day or <20 mg/day) or aerosolized steroid preparations is not a contraindication to varicella vaccination. Persons whose immunosuppressive therapy with steroids has been stopped for 1 month (3 months for chemotherapy) may be vaccinated. In addition, persons with impaired humoral immunity may now be vaccinated. Because children infected with HIV are at greater risk for morbidity from varicella and herpes zoster than are healthy children, the ACIP recommends that, after weighing potential risks and benefits, varicella vaccine should be considered for asymptomatic or mildly symptomatic HIV-infected children in CDC class N1 (no signs or symptoms) or A1 (mild signs or symptoms) with age-specific CD4+ T-lymphocyte percentages of 25%. Eligible children should receive two doses of varicella vaccine, with a 3-month interval between doses. The use of varicella vaccine in other HIV-infected children is being investigated.

Recent Administration of Immune Globulin (IG) or Other Antibody-Containing Blood Products

The effect of the administration of antibody-containing blood products (e.g., IG, whole blood or packed red blood cells, intravenous IG, or varicella zoster IG [VZIG]) on the response to varicella vaccine virus is unknown. Because of the potential inhibition of the response to varicella vaccination by passively transferred antibodies, varicella vaccine should not be administered for at least 5 months after antibody-containing blood products are given. In addition, IG or VZIG should not be administered for 3 weeks following vaccination unless their benefits exceed those of the vaccine. In such cases, the vaccinees should either be revaccinated 5 months later or be tested for immunity 6 months later and revaccinated if seronegative.

No adverse events following varicella vaccination related to the use of salicylates (e.g., aspirin) have been reported to date. However, the manufacturer recommends that vaccine recipients avoid the use of salicylates for 6 weeks after receiving varicella vaccine because of the association between aspirin use and Reye syndrome following varicella.

Although no data exist regarding whether either varicella or live varicella virus vaccine exacerbates tuberculosis, vaccination is not recommended for persons who have untreated active tuberculosis. The effect of varicella vaccine, if any, on tuberculin testing is unknown. However, measles vaccine (and possibly mumps and rubella vaccines) can suppress the response to purified protein derivative (PPD) in a person infected with Mycobacterium tuberculosis. Until additional information is available, it is prudent to apply the same procedures for PPD and measles vaccination to varicella vaccine. If PPD testing is needed, it should be done before MMR or varicella vaccination. PPD testing should be delayed for 4-6 weeks after MMR or varicella vaccination. The PPD may be applied at the same time that MMR or varicella, or both, is administered.

Postexposure Prophylaxis

Use of Vaccine

Administration of varicella vaccine to susceptible children within 72 hours and possibly up to 120 hours after varicella exposure may prevent or significantly modify disease and should be considered in these circumstances. Physicians should advise parents and their children that the vaccine may not protect against disease in all cases. In two controlled studies, protective efficacy was 90% when children were vaccinated within 3 days of exposure.

Use of Varicella Zoster Immune Globulin (VZIG)

Under rare circumstances, VZIG may be recommended for postexposure prophylaxis. The decision to administer VZIG to a person exposed to varicella should be based on 1) whether the patient is susceptible, 2) whether the exposure is likely to result in infection, and 3) whether the patient is at greater risk for complications than the general population (immunocompromised persons, pregnant women, neonates whose mothers had signs and symptoms of varicella within 5 days before and 2 days after delivery, premature infants). VZIG provides maximum benefit when it is administered as soon as possible after the presumed exposure, but it may be effective if administered as late as 96 hours after exposure. VZIG is available in the United States through the American Red Cross; in other countries availability may vary.

Treatment

Acyclovir is an option for treatment of some individuals with varicella. Oral Acyclovir is not recommended for postexposure prophylaxis.

Bibliography

American Academy of Paediatrics. Pickering LK, editor. 2003 Red Book: report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Paediatrics; 2003.
Arvin AM, Gershon AA. Varicella-zoster virus. Cambridge, England: University Press; 2000.
CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunisation Practices (ACIP). MMWR Recomm Rep. 1996;45(RR-11):1-36.
CDC. Prevention of varicella. Updated recommendations of the Advisory Committee on Immunisation Practices (ACIP). MMWR Recomm Rep. 1999;48(RR-6):1-5.
Gershon AA, Takahashi M, Seward J. Varicella vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th ed. Philadelphia: Saunders; 2004. p. 783-823.
Kilgore PE, Kruszon-Moran D, Seward JF, et al. Varicella in Americans from NHANES III: implications for control through routine immunisation. J Med Virol. 2003;70 Supl 1:S111-8.
Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States, 1995-2000. JAMA. 2002;287:606-11.
Whitley RJ. Varicella-zoster virus. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000. p. 1580-6.

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