Varicella / Chickenpox

CDC Yellow Book 2024

Travel-Associated Infections & Diseases

Author(s): Mona Marin, Jessica Leung

INFECTIOUS AGENT: Varicella-zoster virus

ENDEMICITY

Worldwide

TRAVELER CATEGORIES AT GREATEST RISK FOR EXPOSURE & INFECTION

Travelers without evidence of immunity

PREVENTION METHODS

Varicella is a vaccine-preventable disease

DIAGNOSTIC SUPPORT

A clinical laboratory certified in moderate complexity testing; state public health department; or CDC National VZV Laboratory

Infectious Agent

Varicella-zoster virus (VZV) is a member of the Herpesviridae family. Humans are the only VZV reservoir, and disease occurs only in humans. After primary infection as varicella (chickenpox), VZV remains latent in the sensory-nerve ganglia and can reactivate later, causing herpes zoster (shingles).

Transmission

VZV transmission occurs person to person, primarily via the respiratory route, by inhalation of aerosols from vesicular fluid of skin lesions of varicella or herpes zoster; VZV also can spread by direct contact with the vesicular fluid of skin lesions and possibly infected respiratory tract secretions. VZV enters the host through the upper respiratory tract or the conjunctiva. Varicella is a highly contagious viral disease with secondary attack ratios of ≈85% (range 61%–100%) in susceptible household contacts; contagiousness after community exposure is lower. Herpes zoster is ≈20% as infectious as varicella; in susceptible people, contact with herpes zoster rash causes varicella, not herpes zoster.

Virus communicability from patients with varicella begins ≈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; communicability might be longer in immunocompromised people. Vaccinated people who get chickenpox might develop lesions that do not crust. These people are considered contagious until no new lesions have appeared for 24 hours. Patients with herpes zoster are contagious while they have active, vesicular lesions (usually 7–10 days). In utero infection also can occur due to transplacental passage of the virus during maternal varicella infection.

Epidemiology

Varicella occurs worldwide. In temperate climates, varicella tends to be a childhood disease, with peak incidence among preschool and school-aged children; <5% of adults are susceptible to varicella. Disease typically occurs during late winter and early spring. In tropical climates, by contrast, infection tends to be more common later in childhood, with greater susceptibility among adults than in temperate climates, especially in less densely populated areas. The highest incidence of disease in tropical climates occurs during the driest, coolest months.

With the implementation of the childhood varicella vaccination program in the United States in 1996, substantial declines in disease incidence have occurred. Although still endemic, the risk for VZV exposure is now lower in the United States than in most other parts of the world. As of 2019, 18% of countries have introduced a routine varicella vaccination program, and an additional 6% have varicella vaccination programs for risk groups only.

Because varicella is endemic worldwide, all susceptible travelers are at risk for infection 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. Infants, adults, and immunocompromised people without evidence of immunity are at highest risk for severe varicella (see Box 5-08 for acceptable evidence of immunity).

Box 5-08 Acceptable evidence of immunity to varicella

Birth in the United States before 1980 (not acceptable criterion for health care personnel, immunocompromised people, or pregnant people)

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

Health care provider’s diagnosis of varicella or verification of a history of varicella

Health care provider’s diagnosis of herpes zoster or verification of a history of herpes zoster

Laboratory evidence of immunity or laboratory confirmation of disease

Clinical Presentation

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 often is characterized by a short (1- or 2-day) prodromal period (fever, malaise), which might be absent in children, and a generalized pruritic rash. The rash consists of crops of macules, papules, and vesicles (typically 250–500 lesions), which first appear on the chest, back, and face, then spread over the entire body in ≥3 successive waves and resolve by crusting. A characteristic of 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 cerebellar ataxia, encephalitis, hemorrhagic conditions, pneumonia, and secondary bacterial infections of skin lesions, sometimes resulting in bacteremia or sepsis; rarely (≈1 in 40,000 varicella cases), these complications can cause 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 for rash. The rash could be atypical in appearance, with fewer vesicles and predominance of maculopapular lesions. Breakthrough varicella is contagious, although less so than varicella in unvaccinated people.

Diagnosis

Varicella is a nationally notifiable disease in the United States. Often based on an appropriate exposure history and the presence of a generalized maculopapulovesicular rash, the clinical diagnosis of varicella in the United States has become increasingly challenging because a growing number of cases now occur in vaccinated people in whom disease is mild and rash is atypical. Although not routinely performed, laboratory diagnosis is becoming increasingly useful. State public health and commercial laboratories can perform diagnostic tests for laboratory confirmation of varicella. See Collecting Specimens for Varicella-Zoster Virus (VZV) Testing for additional information on specimen collection and testing for varicella.

Nucleic Acid Amplification Testing

For laboratory confirmation, skin lesions are the preferred specimen source. Vesicular swabs or scrapings and scabs from crusted lesions can be used to identify varicella-zoster virus DNA by PCR testing (the preferred method because it is the most sensitive and specific) or direct fluorescent antibody. In the absence of vesicles or scabs, collect scrapings of maculopapular lesions for testing.

Serologic Testing

Serologic tests also can be used to confirm disease but are less reliable than PCR or direct fluorescent antibody methods for virus identification. A substantial 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 might not be reliable in immunocompromised people. Additionally, in vaccinated people, baseline IgG levels might be high; thus, a 4-fold increase in convalescent serum samples might not be achieved. 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. A positive IgM also does not distinguish between primary infection and reactivation.

Treatment

Treatment with antiviral medications is not recommended routinely for otherwise healthy children with varicella. Consider oral acyclovir treatment for people at increased risk for moderate to severe disease (e.g., people >12 years old); people with chronic cutaneous or pulmonary disorders; people who are receiving long-term salicylate therapy; people who are receiving short, intermittent, or aerosolized courses of corticosteroids; and possibly secondary cases among household contacts. Intravenous acyclovir is recommended for immunocompromised people, including patients being treated with high-dose corticosteroids for ≥2 weeks and people with virally mediated complications (e.g., pneumonia). Therapy initiated within 24 hours of illness onset maximizes efficacy. Do not use aspirin or aspirin-containing products to relieve fever from varicella; also avoid ibuprofen, if possible.

Prevention

Vaccine

Indications for Use

In the United States, all people, including those traveling or living abroad, should be assessed for varicella immunity; people who do not have evidence of immunity should receive age-appropriate vaccination if they do not have contraindications to 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 (Box 5-08) should be considered at risk for varicella during international travel.

Administration

Varicella vaccine contains live, attenuated VZV. 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 vaccine for all people aged ≥12 months without evidence of immunity to varicella who do not have contraindications to the vaccine. For children ≥12 months and <13 years, the recommendation is for 2 doses of vaccine administered ≥3 months apart. Typically, the first dose is given at 12–15 months of age and the second at 4–6 years of age. The second dose can be given before age 4, however, provided ≥3 months have passed since the first dose. For people aged ≥13 years, the recommendation is for 2 doses of vaccine administered ≥4 weeks apart. There is no recommendation for varicella vaccination for infants aged <12 months before international travel.

Contraindications

Contraindications to vaccination include allergy to vaccine components, immunocompromising 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 ≈80% after 1 dose and 92%–95% after 2 doses.

Safety & Adverse Reactions

The varicella vaccine is generally well tolerated. The most common adverse events after vaccination are self-limited injection-site reactions (e.g., pain, redness, swelling, soreness). Fever or a varicella-like rash, usually consisting of a few lesions at the injection site or generalized rash with a few lesions, are reported less frequently.

Compared with use of separate MMR and varicella vaccines at the same visit, use of the combination MMRV vaccine is associated with a higher risk for fever and febrile seizures, ≈1 additional febrile seizure for every 2,300–2,600 MMRV vaccine doses administered. Fever and febrile seizures typically occur 5–12 days after the first dose of MMRV; the greatest incidence occurs among children aged 12–23 months. Use of separate MMR and varicella vaccines helps avoid this risk. For detailed information regarding the varicella vaccine, visit CDC’s website, Chickenpox (Varicella) Vaccination.

Postexposure Prophylaxis

Vaccine

CDC recommends administering postexposure varicella vaccine to unvaccinated healthy people aged ≥12 months without other evidence of immunity, to prevent or modify the disease. Administer the vaccine as soon as possible ≤5 days after exposure to rash, if the exposed person has no contraindications. Among children, protective efficacy was reported as ≥90% when vaccination occurred ≤3 days of exposure. Administration of a second postexposure dose is recommended for exposed people who previously received 1 dose, so their vaccinations are current and to best protect against future exposures.

Varicella-Zoster Immune Globulin

CDC recommends that people without evidence of immunity who have contraindications to vaccination and who are at risk for severe varicella and complications 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 people without evidence of immunity, and some neonates and infants. VariZIG provides maximum benefit when administered as soon as possible after exposure, but might be effective if administered as late as 10 days after exposure. In the United States, VariZIG can be obtained from specialty distributors.

If VariZIG is not available, consider administering a single dose (400 mg/kg) of intravenous immune globulin (IVIG) ≤10 days of exposure. In the absence of both VariZIG and IVIG, some experts recommend prophylaxis with acyclovir for people without evidence of immunity who have contraindications to varicella vaccination; the recommended dose is 80 mg/kg/day in 4 divided doses for 7 days, up to a maximum dose of 800 mg 4 times per day, beginning 7–10 days after exposure. Published data on the benefit of acyclovir as postexposure prophylaxis among immunocompromised people are limited.

CDC website: Chickenpox

The following authors contributed to the previous version of this chapter: Mona Marin, Adriana S. Lopez

American Academy of Pediatrics. Varicella-zoster infections. In: Kimberlin DW, Brady MT, Jackson MA, editors. Red Book: 2018 Report of the Committee on Infectious Diseases, 31st edition. Elk Grove Village (IL): American Academy of Pediatrics; 2018. pp. 869–82.

Centers for Disease Control and Prevention. Updated recommendations for use of VariZIG—United States, 2013. MMWR Morb Mortal Wkly Rep. 2013;62(28):574–6.

Leung J, Lopez AS, Mitchell T, Weinberg M, Lee D, Thieme M, et al. Seroprevalence of varicella-zoster virus in five US-bound refugee populations. J Immigrant Minority Health, 2015;17:310–3.

Lopez A, Leung J, Schmid S, Marin M. Varicella. In: Roush SW, Baldy LM, Kirkconnell Hall MA, editors. Manual for the surveillance of vaccine-preventable diseases. Atlanta: Centers for Disease Control and Prevention; 2018. Available from: www.cdc.gov/vaccines/pubs/surv-manual/chpt17-varicella.html.

Lopez AS, Zhang J, Marin M. Epidemiology of varicella during the 2-dose varicella vaccination program – United States, 2005–2014. MMWR Morb Mortal Wkly Rep. 2016;65:902–5.

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Marin M, Guris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1–40.