Varicella-zoster virus, a member of the herpesvirus family. Humans are the only reservoir of the virus, and disease occurs only in humans. After primary infection as varicella (chickenpox), the virus remains dormant in the sensory-nerve ganglia and can reactivate at a later time, causing herpes zoster (shingles).
Varicella-zoster virus is transmitted from person to person, primarily via the respiratory route by inhalation of aerosols from vesicular fluid of skin lesions of varicella or herpes zoster; it can also spread by direct contact with the vesicular fluid of skin lesions and possibly infected respiratory tract secretions. The varicella zoster virus enters the host through the upper respiratory tract or the conjunctiva. Varicella is a highly contagious viral disease with secondary attack ratios of approximately 85% (range, 61%–100%) in susceptible household contacts; contagiousness after community exposure is lower. Herpes zoster is approximately 20% as infectious as varicella; in susceptible people, contact with herpes zoster rash causes varicella, not herpes zoster. The period of communicability of patients with varicella is estimated to begin 1–2 days before the onset of rash and ends when all lesions are crusted, typically 4–7 days after onset of rash in immunocompetent people, but this period may be longer in immunocompromised people. Patients with herpes zoster are contagious while they have active, vesicular lesions (usually 7–10 days).
In utero infection can also occur as a result of transplacental passage of the virus during maternal varicella infection.
Varicella occurs worldwide. In temperate climates, varicella tends to be a childhood disease, with peak incidence among preschool and school-aged children and during late winter and early spring. In these countries, <5% of adults are susceptible to varicella. In tropical climates, the highest incidence was described in the driest, coolest months; overall, infection tends to be acquired later in childhood, resulting in higher susceptibility among adults than in temperate climates, especially in less densely populated areas.
With the implementation of the childhood varicella vaccination program in the United States in 1996, substantial declines have occurred in disease incidence, and, although varicella is still endemic, the risk of exposure to varicella zoster virus is higher in most other parts of the world than it is in the United States.
Because varicella is endemic worldwide, all susceptible travelers are at risk of contracting varicella during travel. Additionally, exposure to herpes zoster poses a risk for varicella in susceptible travelers, although localized herpes zoster is much less contagious than varicella. Travelers at highest risk for severe varicella are infants, adults, and immunocompromised people without evidence of immunity (see criteria for evidence of immunity in “Prevention,” below).
Varicella is generally a mild disease in children, and most people recover without serious complications. The average incubation period is 14–16 days (range, 10–21 days). Infection is often characterized by a short (1- or 2-day) prodromal period (fever, malaise), although this may be absent in children, and a pruritic rash consisting of crops of macules, papules, and vesicles (typically 250–500 lesions), which appear in ≥3 successive waves and resolve by crusting. Characteristic for varicella is the presence of lesions in different stages of development at the same time. Serious complications can occur, most commonly in infants, adults, and immunocompromised people. Complications include secondary bacterial infections of skin lesions sometimes resulting in bacteremia/sepsis, pneumonia, cerebellar ataxia, encephalitis, and hemorrhagic conditions; rarely (about 1 case in 40,000), these complications may result in death.
Modified varicella, also known as breakthrough varicella, can occur in vaccinated people. Breakthrough varicella is usually mild, with <50 lesions, low or no fever, and shorter duration of rash. The rash may be atypical in appearance with fewer vesicles and predominance of maculopapular lesions. Breakthrough varicella is contagious, although less so than varicella in unvaccinated people.
Varicella is often diagnosed clinically on the basis of a generalized maculopapulovesicular rash. The clinical diagnosis of varicella in the United States has become increasingly challenging as a growing proportion of cases occur in vaccinated people in whom disease is mild and rash is atypical. Although not routinely recommended, laboratory diagnosis is likely to become increasingly useful. Varicella is a nationally notifiable disease.
For laboratory confirmation, skin lesions are the preferred specimen. Vesicular swabs or scrapings and scabs from crusted lesions can be used to identify varicella-zoster virus DNA by PCR (preferred method as it is the most sensitive and specific) or direct fluorescent antibody. In the absence of vesicles or scabs, scrapings of maculopapular lesions can be collected for testing. Serologic tests may also be used to confirm disease but are less reliable than PCR or direct fluorescent antibody methods for virus identification.
- A significant rise in serum varicella IgG titers from acute- and convalescent-phase samples by any standard serologic assay can confirm a diagnosis retrospectively; these antibody tests may not be reliable in immunocompromised people.
- Of note, testing for varicella-zoster IgM by using commercial kits is not recommended, because available methods lack sensitivity and specificity; false-positive IgM results are common in the presence of high IgG levels.
Treatment with antivirals is not routinely recommended for otherwise healthy children with varicella. Treatment with oral acyclovir should be considered for people at increased risk for moderate to severe disease, such as people aged >12 years, people with chronic cutaneous or pulmonary disorders, people who are receiving long-term salicylate therapy, and people who are receiving short, intermittent, or aerosolized courses of corticosteroids. Intravenous acyclovir is recommended for immunocompromised people, including patients being treated with high-dose corticosteroids for ≥2 weeks, and people with serious, virally mediated complications (such as pneumonia). Therapy initiated within 24 hours of onset maximizes efficacy.
All people, including those traveling or living abroad, should be assessed for varicella immunity, and those who do not have evidence of immunity or contraindications to vaccination should receive age-appropriate vaccination. Vaccination against varicella is not a requirement for entry into any country (including the United States), but people who do not have evidence of immunity should be considered at risk for varicella during international travel. Evidence of immunity to varicella includes any of the following:
- Documentation of age-appropriate vaccination:
- Preschool-aged children (≥12 months through 3 years of age): 1 dose
- School-aged children (≥4 years of age), adolescents, and adults: 2 doses
- Laboratory evidence of immunity or laboratory confirmation of disease
- Birth in the United States before 1980 (not a criterion for health care personnel, pregnant women, and immunocompromised people)
- A health care provider’s diagnosis of varicella or verification of a history of varicella
- A health care provider’s diagnosis of herpes zoster or verification of a history of herpes zoster
Varicella vaccine contains live, attenuated varicella-zoster virus. Single-antigen varicella vaccine is licensed for people aged ≥12 months, and the combination measles-mumps-rubella-varicella (MMRV) vaccine is licensed only for children 1–12 years. CDC recommends varicella vaccination for all people aged ≥12 months without evidence of immunity to varicella who do not have contraindications to the vaccine: 1 dose for children aged 1–3 years and 2 doses for people aged ≥4 years. The minimum interval between doses is 3 months for children aged <13 years and 4 weeks for people aged ≥13 years. Contraindications for vaccination include allergy to vaccine components, immune-compromising conditions or treatments, and pregnancy. When evidence of immunity is uncertain, a possible history of varicella is not a contraindication to varicella vaccination. Vaccine effectiveness is approximately 80% after 1 dose and 95% after 2 doses.
Vaccine Safety and Adverse Reactions
The varicella vaccine is generally well tolerated. The most common adverse events after vaccination are self-limited injection-site reactions (pain, soreness, redness, and swelling). Fever or a varicellalike rash, usually consisting of a few lesions at the injection site or generalized rash with a small number of lesions, are reported less frequently.
Compared with use of MMR and varicella vaccines at the same visit, use of MMRV vaccine is associated with a higher risk for fever and febrile seizures 5–12 days after the first dose among children aged 12–23 months and approximately 1 additional febrile seizure for every 2,300–2,600 MMRV vaccine doses administered. Use of separate MMR and varicella vaccines avoids this increased risk for fever and febrile seizures in this age group. For detailed information regarding the varicella vaccine, visit www.cdc.gov/vaccines/vpd-vac/varicella/default.htm.
Varicella vaccine is recommended for postexposure administration for unvaccinated healthy people aged ≥12 months and without other evidence of immunity, to prevent or modify the disease. The vaccine should be administered as soon as possible within 5 days after exposure to rash, if there are no contraindications to use. Among children, protective efficacy was reported as ≥90% when vaccination occurred within 3 days of exposure. No data are available regarding a potential benefit of administering a second dose to 1-dose vaccine recipients after exposure. However, administration of the second dose is recommended for exposed people to bring them up-to-date on vaccination and for best protection against future exposures.
Varicella Zoster Immune Globulin
People without evidence of immunity who have contraindications for vaccination and who are at risk for severe varicella and complications are recommended to receive postexposure prophylaxis with varicella zoster immune globulin. The varicella zoster immune globulin product licensed in the United States is VariZIG.
People who should receive VariZIG after exposure include immunocompromised people, pregnant women without evidence of immunity, and some infants. VariZIG provides maximum benefit when administered as soon as possible after exposure but may be effective if administered as late as 10 days after exposure. In the United States, VariZIG can be obtained from FFF Enterprises, Temecula, California, by calling 800-843-7477 or visiting www.fffenterprises.com or from ASD Healthcare, Frisco, Texas, by calling 800-746-6273 or visiting www.asdhealthcare.com.
If VariZIG is not available, intravenous immune globulin (IVIG) can be considered (also within 10 days of exposure). Additionally, in the absence of both VariZIG and IVIG, some experts recommend prophylaxis with acyclovir (80 mg/kg/day in 4 divided doses for 7 days; maximum dose, 800 mg, 4 times per day), beginning 7–10 days after exposure for people without evidence of immunity and with contraindications for varicella vaccination. Published data on the benefit of acyclovir as postexposure prophylaxis among immunocompromised people are limited.
CDC website: www.cdc.gov/chickenpox
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Mona Marin, Adriana S. Lopez